7: Biology of Hair Follicles Flashcards
What is the role of homeobox genes in hair follicle development?
Homeobox genes are responsible for the nonrandom, symmetrical distribution of hair follicles over the body and are involved in patterning during embryonic development.
What are the key signaling pathways involved in the formation of hair placodes?
The key signaling pathways involved in hair placode formation include Wnt, Eda, Fgf, and BMP. These pathways regulate the development and patterning of hair follicles.
How does the WNT/B-catenin pathway influence hair follicle initiation?
The WNT/B-catenin pathway inhibits the degradation of B-catenin, allowing it to translocate to the nucleus and form a complex with LEF/TCF transcription factors, which positively regulates hair follicle initiation and establishes epithelial competence.
What is the significance of Ectodysplasin (EDA) in hair follicle development?
Ectodysplasin (EDA) is related to TNF and EDAR receptors, stimulating early follicle development. Mutations in the EDA gene can lead to X-linked anhidrotic ectodermal dysplasia, resulting in a decreased number of hair follicles and defects in teeth and sweat glands.
What is the function of BMP in hair follicle development?
BMP (bone morphogenetic protein) inhibits follicle formation and placode formation. It plays a role in localizing to early placodes and underlying mesenchyme, with specific BMPs like Bmp2 and Bmp4 having distinct roles in hair follicle development.
Describe the Notch pathway’s role in hair follicle patterning.
The Notch pathway is involved in follicular patterning. Notch delta ligand-1 expressed in the mesenchyme promotes and accelerates placode formation while suppressing placode formation in surrounding cells when misexpressed in a small part of the epithelium.
What is the role of Sonic Hedgehog (SHH) in hair follicle development?
Sonic Hedgehog (SHH) plays a major role in epithelial-mesenchyme signaling. It regulates the proliferation of epithelial cells and the lateral expansion of the follicular placode, promoting the morphogenesis of the dermal papilla.
What are the stages of hair follicle development as described in the text?
The stages of hair follicle development include: 1. Epithelial Placode or Primary Hair Germ - Formation of the epithelial portion of the hair follicle. 2. Bulbous Peg or Hair Bud - Elongation of the hair germ into a cord of epithelial cells, leading to the development of the hair follicle matrix.
A patient presents with a mutation in the EDAR gene. What hair characteristics might you expect, and why?
Variations in the EDAR gene are associated with thicker hair due to its role in early follicle development and follicular patterning.
A researcher is studying mice lacking Noggin. What hair follicle development abnormalities might they observe?
Mice lacking Noggin exhibit fewer hair follicles than normal and delayed follicular development because Noggin is a BMP antagonist that promotes placode development.
How would a loss of dermal β-catenin affect hair follicle development?
Loss of dermal β-catenin results in the arrest of hair follicle development as it is essential for initiating hair follicle formation and establishing epithelial competence.
A patient has a mutation in the EDA gene. What clinical features might you observe?
EDA gene mutations cause X-linked anhidrotic ectodermal dysplasia, characterized by a decreased number of hair follicles, defects in teeth, and sweat glands.
What would happen if the Notch delta ligand-1 is misexpressed in a small part of the epithelium?
Misexpression of Notch delta ligand-1 promotes and accelerates placode formation while suppressing placode formation in surrounding cells, affecting follicular patterning.
A patient lacks Sonic Hedgehog (SHH) signaling. What hair follicle abnormalities might you expect?
Lack of SHH results in extremely defective hair follicles and poorly developed dermal papilla due to its role in epithelial-mesenchyme signaling and dermal papilla morphogenesis.
What is the role of homeobox genes in hair follicle development?
Homeobox genes are responsible for the nonrandom, symmetrical distribution of hair follicles over the body and play a crucial role in patterning during embryonic development.
Describe the Notch pathway’s role in hair follicle patterning.
The Notch pathway is involved in follicular patterning. Notch delta ligand-1, when expressed in the mesenchyme underlying the placode, promotes and accelerates placode formation while suppressing placode formation in surrounding cells when misexpressed.
What are the effects of Noggin in hair follicle development?
Noggin acts as a BMP antagonist, promoting placode development. Mice lacking Noggin exhibit fewer hair follicles than normal and delayed follicular development, highlighting its importance in hair follicle formation.
How does Sonic Hedgehog (SHH) contribute to hair follicle morphogenesis?
Sonic Hedgehog (SHH) plays a major role in epithelial-mesenchyme signaling. It regulates the proliferation of epithelial cells and the lateral expansion of the follicular placode, promoting the morphogenesis of the dermal papilla.
What is the relationship between BMP and hair follicle formation?
BMP (bone morphogenetic protein) inhibits both follicle formation and placode formation. Specific BMPs localize to early placodes and underlying mesenchyme, indicating their regulatory role in hair follicle development.
What is the significance of the dermal papilla in hair follicle development?
The dermal papilla is formed through the condensation of dermal cells beneath the hair follicle placode and is crucial for hair follicle development, providing signals necessary for the growth and maintenance of hair follicles.
How do variations in the EDAR gene affect hair characteristics?
Variations in the EDAR gene are associated with thicker hair. This gene plays a significant role in the development and morphology of hair follicles, influencing hair texture and density.
What is the role of transcription factors in hair follicle development?
Transcription factors such as Lhx2, Sox9, Msx2, and Foxi3 are critical in regulating the signaling pathways (Wnt, Eda, Fgf, BMP) that govern the development and patterning of hair follicles during embryogenesis.
What are the components of the cornified cell envelope in hair follicles?
The components of the cornified cell envelope include: - Loricin - Involucrin - Trichohyaline - Transglutaminases
How does hair follicle formation occur?
Hair follicle formation occurs through: - Repeated processes in several waves - Formation of secondary follicles - Clustering into groups of 3 - Oblique orientation with similar angles to neighboring follicles.
What is the difference in hair follicle characteristics between lanugo, vellus, and terminal hair?
Hair Type | Characteristics |
|———–|—————-|
| Lanugo | Non-pigmented, soft, fine; hair shaft several cms long; shed 32-36th week |
| Vellus | Protrudes slightly from skin surface; diameter <30um; length <2cm |
| Terminal | Thick long hair; diameter >60um; length over 100cm |
What is the role of sex hormones in hair follicle transformation?
Sex hormones influence the transformation of hair follicles by: - Causing the beard area in men to transform into terminal hair follicles - Converting terminal hair follicles in the scalp to vellus-like or miniaturized hair follicles during androgenetic alopecia.
What are the differences in the curvature of hair between curled and straight hair?
The differences in curvature are: - Curled Hair: Curved hair follicles with a more elliptical or flattened cross-section. - Straight Hair: Rounder cross-section. - Mutations in EGFR and IGF binding protein 5 are associated with curly hair in mice.
What is the role of the arrector pili muscle in hair follicle anatomy?
The arrector pili muscle attaches to the bulge area of the hair follicle and is responsible for causing hair to stand on end (goosebumps).
How does the curvature of hair relate to follicle structure?
Curled hair is associated with curved hair follicles, and the cross-section of curled hair is more elliptical or flattened compared to the rounder cross-section of straight hair.
How does the curvature of hair differ between curled and straight hair?
Curled hair has: - Curved hair follicles - A cross-section that is more elliptical or flattened compared to straight hair, which is rounder.
What is the significance of the third bulge in hair follicle development?
The third bulge develops superficial to the sebaceous gland bud and gives rise to the apocrine gland, located in areas such as the axillae and anogenital region.
What is the role of EGF receptor signaling in hair follicle development?
EGF receptor signaling regulates the differentiation of hair follicle cells, influencing the formation and maintenance of the hair follicle structure.
What are the differences in hair types based on their characteristics?
Hair Type | Characteristics |
|———–|—————-|
| Lanugo Hair | Non-pigmented, soft, fine; <30um diameter; <2cm length; shed at 32-36 weeks |
| Vellus Hair | Protrudes slightly from skin surface; >60um diameter; <2cm length |
| Terminal Hair | Thick, long hair; >100cm length; >1 year anagen duration |
What happens to terminal hair follicles in the scalp during androgenetic alopecia?
During androgenetic alopecia, terminal hair follicles in the scalp convert to vellus-like or miniaturized hair follicles under the influence of sex hormones.
What is the structure and function of the outer root sheath in hair follicles?
The outer root sheath is continuous with the epidermis at the infundibulum and extends down to the bulb. It plays a crucial role in protecting the hair follicle and supporting hair growth.
How does the inner root sheath contribute to hair follicle structure?
The inner root sheath extends from the base of the bulb to the isthmus and consists of a companion layer, providing structural support and facilitating hair growth.
What is the significance of the infundibulum in hair follicle anatomy?
The infundibulum resembles epithelial keratinization and forms a granular layer, playing a key role in the overall structure and function of the hair follicle.
What are the differences in hair bulb location during the anagen phase for different hair types?
Hair Type | Hair Bulb Location During Anagen |
|———–|——————————-|
| Lanugo Hair | Reticular dermis |
| Vellus Hair | Subcutaneous fat |
| Terminal Hair | Subcutaneous fat |
What is the role of keratin associated proteins in hair progenitor cells?
Keratin associated proteins in hair progenitor cells are essential for the structural integrity and function of hair follicles, contributing to hair shaft differentiation.
How does the anagen duration differ among various hair types?
Hair Type | Anagen Duration |
|———–|—————-|
| Lanugo Hair | 1-3 months |
| Vellus Hair | 1-2 weeks |
| Terminal Hair | >1 year (if miniaturized: <1 week) |
What is the relationship between hair follicle formation and sex hormones?
Hair follicle formation in areas such as the beard is influenced by sex hormones, leading to the transformation of hair types and characteristics.
What are the characteristics of the lower follicle in hair anatomy?
The lower follicle is responsible for regenerating with each hair follicle cycle, playing a crucial role in hair growth and renewal.
What is the significance of the isthmus in hair follicle anatomy?
The isthmus is where trichilemmal keratinization occurs, and it lacks a granular layer, contributing to the overall structure of the hair follicle.
How do mutations in EGFR and IGF binding protein affect hair texture?
Mutations in EGFR and IGF binding protein 5 can lead to curly hair in mice, indicating a genetic influence on hair texture and follicle shape.
What is the role of the companion layer in the inner root sheath?
The companion layer in the inner root sheath supports the hair follicle structure and aids in the differentiation of hair follicle cells.
How does hair follicle formation occur in waves?
Hair follicle formation occurs in repeated waves, leading to the development of secondary follicles and clustering into groups of three.
What is the function of the arrector pili muscle in hair follicles?
The arrector pili muscle attaches to the bulge area of hair follicles, causing hair to stand up and playing a role in thermoregulation and emotional responses.
What are the differences in central medulla presence among hair types?
Hair Type | Central Medulla Presence |
|———–|————————|
| Lanugo Hair | Without medulla |
| Vellus Hair | With medulla |
| Terminal Hair | With medulla |
What is the significance of the bulge area in hair follicle anatomy?
The bulge area is significant as it is where the arrector pili muscle attaches and plays a role in the regeneration and growth of hair follicles.
How does hair shaft differentiation occur in hair follicles?
Hair shaft differentiation involves specific keratins such as Krt 31-37 and Krt 81-86, which are crucial for the structural integrity of the hair shaft.
What is the relationship between hair follicle types and their locations on the body?
Hair follicle types vary in location: - Lanugo Hair: Found at puberty in genitalia, axilla, trunk. - Vellus Hair: Present at birth in scalp, brows, eyelashes. - Terminal Hair: Develops in various body areas influenced by hormones.
What is the role of glycogen in the hair follicle?
Glycogen is abundant in the hair follicle, particularly in the isthmus area, providing energy for the cells involved in hair growth and maintenance.
How does the diameter of hair types differ?
Hair Type | Diameter |
|———–|———-|
| Lanugo Hair | <30um |
What are the types of hair?
- Vellus Hair: Present at birth in scalp, brows, eyelashes.
- Terminal Hair: Develops in various body areas influenced by hormones.
How does the diameter of hair types differ?
Hair Type | Diameter |
|———–|———-|
| Lanugo Hair | <30um |
| Vellus Hair | >60um |
| Terminal Hair | Thick, varies |
What is the impact of sex hormones on hair follicle transformation?
Sex hormones influence the transformation of hair follicles, particularly in areas like the beard, leading to the development of terminal hair follicles.
What is the significance of the granular layer in the infundibulum?
The granular layer in the infundibulum resembles epithelial keratinization and is important for the structural integrity of the hair follicle.
How does hair follicle orientation affect hair growth?
Hair follicles are oriented obliquely with a similar angle to neighboring follicles, which can influence the overall appearance and growth pattern of hair.
What is the relationship between hair follicle types and their shedding patterns?
Different hair types have varying shedding patterns:
- Lanugo Hair: Shed at 32-36 weeks.
- Vellus Hair: Shorter shedding duration.
- Terminal Hair: Longer anagen duration, leading to less frequent shedding.
What is the role of the epidermal keratin in hair follicles?
Epidermal keratin (Krt 1/10) is crucial for the structural integrity of hair follicles, contributing to the overall health and function of hair.
How does the structure of the hair follicle change during the anagen phase?
During the anagen phase, the hair follicle undergoes significant growth and differentiation, leading to the formation of a mature hair shaft and supporting structures.
What are the main layers of the hair follicle and their characteristics?
Layer | Characteristics |
|——-|—————-|
| Henle Layer | One cell layer thick, first to develop keratohyalin granules, first to keratinize |
| Huxley Layer | Two to four cell layers thick, keratinizes above Henle layer, contains Fluegelzellen (wing cells) |
| Inner Root Sheath Cuticle | Shingled roof appearance, anchors hair shaft to follicle, contains hard keratins and proteins |
| Companion Layer | Innermost layer of outer root sheath, provides slippage plane, cells express type 2 cytokeratin K6hf |
| Hair Shaft | Comprises bulk of the shaft, contains melanin, has a cuticle that endures weathering, cortex with macrofibrils and microfibrils, medulla at center of larger hairs |
What is the role of the dermal papilla in hair follicle development?
- Mesenchymally derived tissue
- Contains fibroblasts, collagen bundles, mucopolysaccharide-rich stroma, nerve fibers, and a single capillary loop.
- Induces hair follicle formation when transplanted onto non-hair-bearing epidermis.
- Volume correlates with:
- Number of matrix cells
- Resulting size of hair shaft
- Produces KGF (Keratinocyte Growth Factor), necessary for hair growth and cycling.
How do neurotrophic factors influence hair follicle cycling?
- Produced by hair follicle keratinocytes and Merkel cells.
- Influence perifollicular nerves to stimulate remodeling in a hair cycle-dependent manner.
- Neurotrophic factors include cytokines and regulatory molecules that affect hair follicle health and regeneration.
What is the significance of Shh in hair follicle innervation?
- Shh (Sonic Hedgehog) is produced by nerve fibers innervating hair follicles.
- Plays a role in healing skin wounds.
- Signals bulge cells marked by Hedgehog response gene Gli1 to change lineage into epidermal stem cells.
- Contributes to wound healing by maintaining bulge cells capable of becoming epidermal stem cells.
What is the significance of the dermal papilla volume in hair follicle development?
Dermal papilla volume correlates with the number of matrix cells and the resulting size of the hair shaft, influencing hair growth and cycling.
How does the inner root sheath cuticle contribute to hair shaft anchoring?
The inner root sheath cuticle has a shingled roof appearance that intertwines with the cuticle cells of the hair shaft, anchoring it tightly to the follicle.
How does the absence of SHH signaling affect wound healing?
SHH signaling is crucial for healing skin wounds as it signals bulge cells to change lineage into epidermal stem cells.
What is the role of the perineural niche in wound healing?
The perineural niche maintains bulge cells capable of becoming epidermal stem cells, contributing to wound healing.
How does the dermal papilla contribute to hair follicle formation when transplanted?
The dermal papilla has powerful inductive properties and can induce hair follicle formation when transplanted onto non-hair-bearing epidermis.
What is the role of keratinocyte growth factor (KGF) in hair growth?
KGF, produced by anagen dermal papilla, is necessary for hair growth and cycling.
What is the role of the Companion Layer in hair follicle structure?
The Companion Layer is the innermost layer of the outer root sheath, providing a slippage plane that moves upward with the rest of the inner root sheath. Its cells are flat and express type 2 cytokeratin K6hf, while the outer root sheath consists of cuboidal cells.
How does the Henle Layer contribute to hair follicle development?
The Henle Layer is one cell layer thick and is the first to develop keratohyalin granules, playing a crucial role in the keratinization process of hair follicles.
What is the significance of the Dermal Papilla in hair follicle formation?
The Dermal Papilla is mesenchymally derived tissue that has powerful inductive properties, capable of inducing hair follicle formation when transplanted onto non-hair-bearing epidermis. Its volume correlates with the number of matrix cells and the resulting size of the hair shaft.
Describe the Huxley Layer and its function in hair follicles.
The Huxley Layer consists of two to four cell layers thick, keratinizing above the Henle layer, and contains Fluegelzellen or wing cells that protrude through the Henle Layer, attaching to the companion layer, thus contributing to the structural integrity of the hair follicle.
What is the function of GATA 3 in hair follicle development?
GATA 3 is involved in the differentiation and lineage of hair shaft cells, playing a critical role in the development and maintenance of hair follicles.
How do neurotrophic factors influence hair follicle cycling?
Neurotrophic factors, produced by hair follicle keratinocytes and Merkel cells, influence perifollicular nerves to stimulate remodeling in a hair cycle-dependent manner, affecting hair growth and cycling.
What is the relationship between Substance P and hair follicle keratinocytes?
Substance P, contained in perifollicular nerves, influences follicular keratinocytes and alters hair follicle cycling, indicating its role in hair growth regulation.
Explain the role of Shh in hair follicle development and wound healing.
Shh, produced by nerve fibers innervating hair follicles, signals bulge cells marked by the Hedgehog response gene Gli1 to change lineage into epidermal stem cells, contributing to wound healing and maintaining bulge cells capable of becoming epidermal stem cells.
What is the significance of the Inner Root Sheath Cuticle in hair follicles?
The Inner Root Sheath Cuticle has a shingled roof appearance that overlaps and intertwines with the cuticle cells of the hair shaft, anchoring the hair shaft tightly to the follicle and influencing hair shape.
How does the Cortex of the hair shaft contribute to its properties?
The Cortex comprises the bulk of the hair shaft, contains melanin, and is structured with macrofibrils arranged in large cable-like structures and microfibrils composed of intermediate filaments, contributing to the hair’s strength and color.
What is the role of KGF (Keratinocyte Growth Factor) in hair follicle cycling?
KGF, produced by the anlagen dermal papilla, is necessary for hair growth and cycling, influencing the proliferation and differentiation of hair follicle keratinocytes.
Describe the Medulla and its function in larger hairs.
The Medulla is the center of larger hairs and is under the control of androgens, playing a role in the overall structure and characteristics of the hair shaft.
What is the function of Merkel cells in hair follicle innervation?
Merkel cells are neuroendocrine cells that produce neurotrophic factors, cytokines, and regulatory molecules, influencing the sensory perception and remodeling of hair follicles.
How does the Cortex differ from the Cuticle in hair structure?
The Cortex comprises the bulk of the hair shaft and contains melanin and macrofibrils, while the Cuticle is the outermost layer that endures weathering and is often lost in the distal ends of long hairs.
What is the role of FGF receptor 2 in hair follicle development?
FGF receptor 2 is found in matrix keratinocytes and is essential for the signaling pathways that regulate hair follicle development and cycling.
How do myelinated nerve fibers contribute to hair follicle function?
Myelinated nerve fibers run parallel to hair follicles and are involved in sensory functions, influencing the growth and cycling of hair follicles through their interactions with follicular keratinocytes.
What is the significance of the Prekeratogenous zone in hair shaft development?
The Prekeratogenous zone is where specific hair shaft keratins are expressed, and it plays a crucial role in the differentiation of hair shaft cells, influencing the overall structure of the hair.
How does the Dermal Papilla influence hair follicle size?
The volume of the Dermal Papilla correlates with the number of matrix cells and the resulting size of the hair shaft, indicating its critical role in determining hair follicle size and health.
What is the function of pilo-Ruffini endings in hair follicles?
Pilo-Ruffini endings are sensory receptors that detect tension in hair follicles, contributing to the sensory feedback mechanisms associated with hair growth and follicle health.
How does BMP receptor type 1a affect hair shaft development?
BMP receptor type 1a is involved in the differentiation of matrix cells into hair shaft cells, playing a significant role in the development and structure of the hair shaft.
What is the role of hard keratins in hair follicles?
Hard keratins and associated proteins dictate hair shape by funneling the hair shaft cells, contributing to the overall structure and resilience of the hair.
How do free nerve endings contribute to hair follicle function?
Free nerve endings are responsible for detecting pain in hair follicles, playing a role in the sensory feedback and protective mechanisms associated with hair growth.
What is the relationship between hair follicle innervation and hair growth?
Hair follicle innervation, through various nerve endings and neurotrophic factors, influences the cycling and growth of hair follicles, indicating a complex interaction between the nervous system and hair biology.
How does the Huxley Layer interact with the Henle Layer?
The Huxley Layer, which is thicker than the Henle Layer, keratinizes above it and contains wing cells that protrude through the Henle Layer, attaching to the companion layer, thus maintaining the structural integrity of the hair follicle.
What is the significance of neuroendocrine cells in hair follicle function?
Neuroendocrine cells produce neurotrophic factors, cytokines, and regulatory molecules that influence hair follicle cycling and the response of follicular keratinocytes to various stimuli.
How does GATA 3 influence hair follicle lineage?
GATA 3 plays a crucial role in the differentiation and lineage of hair shaft cells, influencing the development and maintenance of hair follicles throughout their life cycle.
What is the role of Lef-1 transcription factor in hair shaft differentiation?
Lef-1 transcription factor is essential for the differentiation of hair shaft cells, indicating its importance in the development of the hair structure.
How does the Medulla affect the characteristics of larger hairs?
The Medulla, being the center of larger hairs, contributes to their overall structure and is influenced by androgens, which can affect hair thickness and growth patterns.
What is the impact of CGRP on hair follicle activity?
CGRP, contained in perifollicular nerves, influences follicular keratinocytes and alters hair follicle cycling, indicating its role in hair growth regulation.
How does the cuticle of hair shafts contribute to their durability?
The cuticle, being the outermost layer of the hair shaft, endures weathering and protects the inner layers, contributing to the overall durability and resilience of the hair.
What is the function of fluegelzellen in hair follicles?
Fluegelzellen, or wing cells, are protruding cells from the Huxley Layer that attach to the companion layer, contributing to the structural integrity and function of the hair follicle.
How does hair follicle innervation affect skin wound healing?
Hair follicle innervation, particularly through Shh signaling, contributes to skin wound healing by maintaining bulge cells capable of becoming epidermal stem cells, thus facilitating tissue repair.
What is the significance of the anagen phase in the hair follicle cycle?
The anagen phase is crucial for hair growth, determining the final length of hair. It varies according to body site, with scalp hair having the longest anagen duration (2 to more than 8 years). During this phase, 90-93% of scalp follicles are actively growing, with a growth rate of approximately 0.37mm-0.44mm per day (1cm/month).
What are the stages of the anagen phase in hair follicle development?
The stages of the anagen phase are as follows:
1. Stage I: Growth of the dermal papilla; onset of mitotic activity in the germlike overlying epithelium.
2. Stage II: Bulb matrix cells envelop the dermal papilla and begin differentiation; evolving bulb begins descent along the fibrous streamer.
3. Stage III: Bulb matrix cells show differentiation into all follicular components.
4. Stage IV: Matrix melanocytes reactivate.
5. Stage V: Hair shaft emerges and dislodges telogen hair.
6. Stage VI: New hair shaft emerges from skin surface.
7. Stage VII: Stable growth.
What occurs during the catagen phase of the hair follicle cycle?
During the catagen phase, the following events occur:
- Cessation of mitotic activity in the matrix cells and coordinated apoptosis in the cyclic portion of the hair follicle.
- The lower follicle retracts upward with the dermal papilla.
- The perifollicular sheath collapses, forming a fibrous streamer composed of fibroblasts, small blood vessels, and collagen.
- Melanocyte activity ceases, and melanin is engulfed by macrophages.
- The bulb shortens and the dermal papilla migrates upward, which is necessary for continued follicle cycling.
What role do hair follicle stem cells play in hair follicle regeneration?
Hair follicle stem cells are crucial for regeneration as they are permanently located in the bulge of the hair follicle. They give rise to all epithelial layers of the hair follicle and migrate into wounds during reepithelialization. Loss of these stem cells can lead to permanent or cicatricial types of alopecia.
How does the Fgf5 gene influence hair growth?
The Fgf5 gene is known to regulate the duration of the anagen phase, influencing hair growth by determining how long hair follicles remain in the growth phase.
How does the Fgf5 gene influence hair growth and the hair follicle cycle?
The Fgf5 gene influences hair growth by regulating the length of the hair cycle. Mice with a mutation in this gene exhibit hair that is 50% longer than their wild-type counterparts, leading to an angora phenotype. This gene may also trigger the onset of the catagen phase, thus playing a significant role in hair follicle cycling.
What is the role of the dermal papilla during the anagen phase?
During anagen, the dermal papilla moves downward, and endothelial proliferation and angiogenesis occur, marking the restoration of the lower follicle.
How does the transition from anagen to catagen affect hair follicle structure?
The transition involves cessation of mitotic activity in matrix cells, apoptosis in the cyclic portion of the follicle, and upward retraction of the lower follicle with the dermal papilla.
What is the role of FGF-5 in hair follicle cycling?
FGF-5 triggers the onset of catagen, and its absence results in hair that is 50% longer than normal, as seen in the angora phenotype.
How does the expression of keratin 6 relate to wound healing?
Keratin 6 is expressed during wound healing and is involved in the proliferation and migration of keratinocytes into the dermis.
What is the role of Stat3 in hair follicle cycling?
Stat3 regulates cell migration and is essential for hair follicles to enter the anagen phase.
How does the absence of TGF-α affect hair follicle development?
Lack of TGF-α results in abnormal hair follicle development, manifesting as a waved hair phenotype.
What is the role of the secondary germ in hair follicle cycling?
The secondary germ is a transient structure formed at the end of catagen that contributes to the regeneration of the lower follicle during anagen.
What is the significance of the anagen phase in the hair follicle cycle?
The anagen phase is crucial for hair growth, determining the final length of hair. It varies by body site, with scalp hair having the longest anagen duration (2 to over 8 years). During this phase, 90-93% of scalp follicles are actively growing, with a growth rate of approximately 0.37mm to 0.44mm per day.
Describe the role of hair follicle stem cells during the hair follicle cycle.
Hair follicle stem cells, located in the bulge, are essential for the regeneration of hair follicles. They give rise to all epithelial layers of the hair follicle and migrate into wounds during reepithelialization. Loss of these stem cells can lead to permanent or cicatricial types of alopecia.
What are the stages of the anagen phase and their significance?
The stages of the anagen phase are as follows:
- Stage I: Growth of the dermal papilla; onset of mitotic activity in the overlying epithelium.
- Stage II: Bulb matrix cells envelop the dermal papilla and begin differentiation; bulb descends along the fibrous streamer.
- Stage III: Bulb matrix cells differentiate into all follicular components.
- Stage IV: Matrix melanocytes reactivate.
- Stage V: Hair shaft emerges and dislodges telogen hair.
- Stage VI: New hair shaft emerges from the skin surface.
- Stage VII: Stable growth.
These stages are critical for the proper development and cycling of hair follicles.
What happens during the catagen phase of the hair follicle cycle?
During the catagen phase, there is a cessation of mitotic activity in matrix cells, leading to well-coordinated apoptosis. The lower follicle retracts upward, and the dermal papilla moves downward. This phase marks the transition from active growth to rest, with the formation of a fibrous streamer and the engulfment of melanin by macrophages.
How does the telogen phase contribute to the hair follicle cycle?
The telogen phase is a resting period for hair follicles. During this phase, the lower follicle retracts upward, and the dermal papilla is protected from apoptosis. It is essential for the cycling of hair follicles, allowing for the shedding of old hair and the preparation for new hair growth in the subsequent anagen phase.
What is the role of the Fgf5 gene in hair follicle cycling?
The Fgf5 gene plays a significant role in hair follicle cycling by influencing the length of hair. Mutations in this gene can result in hair that is 50% longer than wild-type, leading to an angora phenotype. It may also trigger the onset of the catagen phase, thus regulating the transition between growth and rest phases.
Explain the significance of TGF-α in hair follicle development based on mouse studies.
In mouse studies, TGF-α is identified as the major ligand for EGFR (Epidermal Growth Factor Receptor). A lack of TGF-α results in abnormal hair follicle development, manifesting as a waved hair phenotype. This indicates that TGF-α is crucial for normal hair follicle cycling and development.
What are the implications of the dermal papilla’s migration during the hair follicle cycle?
The migration of the dermal papilla from the subcutaneous fat to the dermis during catagen is necessary for continued follicle cycling. This movement ensures that the dermal papilla is positioned correctly for the next anagen phase, facilitating the regeneration of hair follicles and maintaining hair growth.
How do stem cell markers like Lgr5 and Lgr6 contribute to hair follicle biology?
Stem cell markers such as Lgr5 and Lgr6 are crucial for identifying and understanding hair follicle stem cells. Lgr5 marks exclusive secondary germ cells in the bulge, while Lgr6 is found above the bulge in the upper isthmus, indicating cells that migrate to the epidermis during homeostasis and after wounding, thus playing a role in hair follicle regeneration and repair.
What is the clinical significance of understanding the hair follicle cycle?
Understanding the hair follicle cycle is clinically significant for developing treatments for hair loss conditions such as alopecia. By targeting specific phases of the cycle, therapies can be designed to enhance hair growth, prolong the anagen phase, or effectively manage the transition to catagen and telogen phases, improving patient outcomes in hair restoration.
What factors can induce premature catagen development in hair follicles?
- TGF-β1: Induces premature catagen in isolated human hair follicles.
- Neurotrophin-3 and brain-derived neurotrophic factor: Contribute to premature catagen development, leading to a shortening of hair length by 15%.
What is the role of Notch signaling in melanocyte stem cells?
Notch signaling prevents apoptosis of melanocyte stem cells and immature melanoblasts, playing a crucial role in maintaining the population of these cells during hair follicle morphogenesis.
What are the two sources of melanoblasts during hair melanocyte development?
- Neural crest cells migrating in the dorsolateral pathway.
- Schwann cell progenitors in cutaneous nerves.
What is the significance of Bcl-2 in melanocyte stem cells?
Bcl-2 plays a key role in the maintenance of melanocyte stem cells. Bcl2 knockout in mice leads to progressive hair graying due to depletion of melanocyte stem cells, but this deficiency can be compensated by overexpression of SCF.
What happens during the telogen phase of hair follicles?
- Club hair is formed.
- About 1% of telogen hairs are shed each day.
- Exogen: A separate phase for hair shedding occurs.
- Immediate telogen release can happen after starting medications (like minoxidil) or due to rapid fluctuations in light-dark cycles, leading to increased shedding of club hairs.
How does TGF-β1 influence hair follicle cycling?
TGF-β1 induces premature catagen, leading to shortened hair length and early cessation of growth.
What is the significance of the lag period in telogen?
The lag period is the time between hair shedding and regrowth, lasting several months in conditions like androgenetic alopecia.
What is the role of melanocyte stem cells during the telogen phase?
During telogen, melanocyte stem cells are quiescent, located in the bulge, and do not express Trp1 or tyrosinase.
How does Wnt activation affect melanocyte stem cells (MCSCs)?
Wnt activation in MCSCs promotes their differentiation into pigment-producing melanocytes.
What is the role of Bcl-2 in melanocyte stem cell maintenance?
Bcl-2 prevents apoptosis of melanocyte stem cells, and its knockout leads to progressive hair graying due to stem cell depletion.
How does immediate telogen release affect hair shedding?
Immediate telogen release occurs after starting medications like minoxidil or due to rapid light–dark cycle fluctuations, leading to increased shedding of club hairs.
What is the role of Pax3 in melanocyte development?
Pax3 stimulates dopachrome tautomerase, an early melanoblast marker, and is essential for melanin biosynthesis.
What is the significance of the club hair formation during the telogen phase?
- Club hair is formed as about 1% of telogen hairs are shed each day.
- The exogen phase is a separate phase for hair shedding, which occurs after the immediate telogen release triggered by factors like medications (e.g., minoxidil) or light-dark cycle fluctuations.
Describe the migration process of melanoblasts during hair melanocyte development.
- Melanoblasts originate in the neural crest and migrate to the dermis, then to the epidermis.
- They enter the placode of the developing hair follicle and proliferate to produce pigment synchronously with hair fiber formation.
What role does SCF/c-kit signaling play in melanocyte development?
SCF/c-kit signaling is crucial for the migration of melanoblasts and their differentiation into pigment-producing melanocytes.
How does TGF-β signaling affect melanocyte stem cells during hair follicle morphogenesis?
TGF-β signaling plays an important role in controlling melanocyte stem cells, facilitating their entry into a noncycling (dormant) state during hair follicle morphogenesis.
What is the impact of Bcl-2 on melanocyte stem cells?
Bcl-2 is key in maintaining melanocyte stem cells; its knockout in mice leads to progressive hair graying due to depletion of these cells. Bcl-2 deficiency can be compensated by overexpression of SCF, which rescues melanocyte stem cells in the hair follicle bulge.
What changes occur in melanocytes during the telogen phase of the hair cycle?
- In the telogen phase, hair follicle melanocytes are found in the bulge, secondary hair germ, and connective tissue.
- They do not express Trp1 and tyrosinase and do not proliferate, remaining in a quiescent state until reactivated.
What is the function of Foxn1 in melanocyte function?
Foxn1 is produced by pigment recipient keratinocytes and helps identify targets for pigment transfer by interacting with its target Fgf2.
How do melanocyte stem cells (McSCs) respond to wounding or UVB irradiation?
After wounding or UVB irradiation, McSCs can exit the stem cell niche, migrate to the epidermis, and differentiate into functional epidermal melanocytes, aided by Mc1r signaling.
What are the consequences of mutations in the Endothelin receptor type B (Ednrb) and C-kit receptor?
Mutations in Endothelin receptor type B (Ednrb) are associated with Hirschsprung disease, while mutations in the C-kit receptor lead to piebaldism, affecting melanocyte development and pigmentation.
What is the role of Notch signaling in melanocyte development?
Notch signaling prevents apoptosis of melanocyte stem cells and immature melanoblasts, ensuring their survival and proper development during hair follicle morphogenesis.
What is the lag period in hair shedding and regrowth, particularly in patients with androgenetic alopecia?
The lag period refers to the time between hair shedding and regrowth, which lasts several months in patients with androgenetic alopecia, indicating a delay in the hair cycle.
How does the hair follicle cycle influence the behavior of melanocytes?
During the anagen phase, resting melanocytes proliferate, differentiate, and migrate within the hair follicle, synchronously regenerating the hair follicle bulb.
What is the significance of the melanocortin 1 receptor (Mc1r) in melanocyte function?
Mc1r is crucial for the exit of melanocyte stem cells from the niche, allowing them to migrate to the epidermis and differentiate into functional melanocytes, especially after stimuli like wounding or UV exposure.
What are the implications of Bcl-2 knockout in mice regarding hair pigmentation?
Bcl-2 knockout in mice leads to a depletion of melanocyte stem cells, resulting in progressive hair graying, highlighting the importance of Bcl-2 in melanocyte survival and function.
What is the role of Pax3 and microphthalmia transcription factors (Mitf) in melanocyte development?
Pax3 and Mitf stimulate Dopachrome tautomerase (Tyrosinase-related protein 2), which is essential for melanin biosynthesis and serves as an early marker for melanoblasts.
How does the hair cycle affect the expression of melanogenic enzymes in melanocytes?
During the telogen phase, melanocytes do not express key enzymes like Trp1 and tyrosinase, while in the anagen phase, they actively proliferate and differentiate, expressing these enzymes for pigment production.
What is the relationship between neurotrophic factors and hair follicle transformation?
Neurotrophic factors like neurotrophin-3 play a role in hair follicle transformation by influencing the transition from anagen to catagen, affecting hair growth and pigmentation.
What are the characteristics of unpigmented hairs and their genetic implications?
Unpigmented hairs can result from mutations in the Endothelin receptor type B (Ednrb) or C-kit receptor, as well as genetic ablation of SCF or c-kit, leading to conditions like Hirschsprung disease and piebaldism.
What is the role of signaling molecules like c-kit and Ednrb in melanocyte function?
Signaling molecules such as c-kit and Ednrb are expressed at low levels in melanocyte stem cells and are crucial for their maintenance and function during hair follicle morphogenesis.
How does the hair follicle cycle influence the differentiation of melanocyte stem cells?
The hair follicle cycle regulates the differentiation of melanocyte stem cells, with Wnt activation promoting their differentiation into pigment-producing melanocytes during the anagen phase.
What is the significance of the immediate telogen release in hair shedding?
Immediate telogen release occurs after starting medications like minoxidil or due to rapid fluctuations in light-dark cycles, leading to an increase in shedding of club hairs within weeks of the precipitating event.
What are the clinical implications of understanding hair follicle melanocyte stem cells?
Understanding hair follicle melanocyte stem cells can inform treatments for hair loss and pigmentation disorders, as their maintenance and differentiation are crucial for hair health and color.
How does the presence of melanocytes in the hair bulb contribute to hair pigmentation?
Melanocytes in the hair bulb synthesize and transport melanin to hair shaft keratinocytes, which is essential for the pigmentation of hair.
What are the effects of TGF-β signaling on melanocyte stem cells during the hair cycle?
TGF-β signaling activates melanocyte stem cells when they reenter the quiescent noncycling state during the hair cycle, requiring Bcl2 for cell survival.
What is the role of neurotrophic factors in the development of hair follicles?
Neurotrophic factors are involved in the signaling pathways that regulate the transition of hair follicles between different growth phases, influencing hair growth and pigmentation.
How does the hair cycle affect the behavior of melanocytes in terms of proliferation and differentiation?
During the anagen phase, melanocytes proliferate and differentiate, while in the telogen phase, they remain quiescent and do not proliferate, indicating a cyclical pattern of activity.
What are the potential consequences of Bcl-2 deficiency in melanocyte stem cells?
Bcl-2 deficiency can lead to the depletion of melanocyte stem cells, resulting in hair graying and loss of pigmentation, highlighting its critical role in cell survival.
What is the role of SCF/c-kit signaling in hair follicle melanocyte repopulation?
SCF/c-kit signaling plays a critical role in the repopulation of the hair follicle bulb with pigment-producing melanocytes. Overexpression of SCF increases the number of hair follicle melanocytes and their proliferative activity. Blocking c-kit signaling reduces the melanocyte number in anagen hair follicles, leading to hair depigmentation.
How does aging affect melanocyte activity in hair follicles?
Aging leads to premature loss and graying of hair, characterized by fewer melanocytes in the bulb of gray hair. Although these melanocytes still express tyrosinase and synthesize melanin, they transfer less melanin to keratinocytes. Additionally, melanocyte stem cells in the outer root sheath are markedly reduced in gray hairs, and these stem cells are damaged with age.
What is the significance of the MC-1R pathway in melanocyte function?
The MC-1R pathway is crucial for controlling hair color and the balance between black and yellow pigment synthesis (eumelanin and pheomelanin). It is expressed by hair follicle melanocytes and its ligands, α-MSH and ACTH, promote melanocyte proliferation, dendricity, and pigment production. Additionally, β-endorphin also promotes these functions and modulates the activity of protein kinase C, a positive regulator of pigment production.
What are the essential co-factors for melanogenic enzymes?
The essential co-factors for melanogenic enzymes include: 1. 6-tetrahydrobiopterin 2. Tyrosinase-related proteins 1/2 3. Glutamyltranspeptidase 4. Peroxidase
What happens to melanocyte stem cells in gray hair?
In gray hair, melanocyte stem cells are damaged, leading to a marked reduction in their numbers. This damage contributes to the premature differentiation of melanocytes, resulting in the loss of pigmentation in hair.
What would be the effect of blocking c-kit signaling with an antibody like ACK45?
Blocking c-kit signaling reduces melanocyte numbers in anagen hair follicles, leading to hair depigmentation.
How does the SCF/c-kit signaling pathway affect melanocyte activity in hair follicles?
The SCF/c-kit signaling pathway is critical for repopulating the bulb with pigment-producing melanocytes and increasing their proliferative activity.
What role does the melanocortin type 1 receptor (MC-1R) play in hair pigmentation?
MC-1R controls hair color by balancing black (eumelanin) and yellow (pheomelanin) pigment synthesis.
What is the role of BMP signaling in pheomelanin synthesis?
BMP signaling positively regulates ASP expression, which inhibits MC-1R signaling, leading to pheomelanin synthesis.
How does aging affect melanocyte activity in hair follicles?
Aging leads to fewer melanocytes in the bulb of gray hair, reduced melanoblasts and stem cells in the outer root sheath, and damage to melanocyte stem cells.
What is the role of ATM-kinase in melanocyte stem cells?
ATM-kinase protects melanocyte stem cells from premature differentiation by acting as a central transducer of the DNA-damage response.
How does the Notch signaling pathway prevent premature differentiation of melanoblasts?
Notch signaling prevents differentiation of melanoblasts into pigment-producing melanocytes before they reach the hair bulb, ensuring proper positioning in the hair matrix.
What happens to melanocytes during the catagen phase?
During catagen, melanogenic activity ceases, some pigment-producing melanocytes undergo apoptosis, and others drop into the dermal papilla.
How does the Proopiomelanocortin (POMC)–MC-1R pathway affect melanocytes?
The POMC–MC-1R pathway promotes melanocyte proliferation, dendricity, and pigment production through ligands like α-MSH and ACTH.
What is the role of β-endorphin in hair pigmentation?
β-endorphin promotes melanocyte proliferation, dendricity, and pigment production by binding to μ-opiate receptors and modulating protein kinase C activity.
What role does Notch signaling play in the differentiation of melanoblasts into pigment-producing melanocytes?
Notch signaling prevents the differentiation of melanoblasts into pigment-producing melanocytes before they reach the hair bulb, ensuring proper positioning in the hair matrix.
How does SCF/c-kit signaling influence the population of melanocytes in hair follicles?
SCF/c-kit signaling is critical for the repopulation of the hair bulb with pigment-producing melanocytes. Overexpression of SCF increases the number of hair follicle melanocytes and their proliferative activity, while blocking c-kit signaling reduces melanocyte numbers in anagen hair follicles, leading to hair depigmentation.
What is the significance of the MC-1R receptor in hair color determination?
The melanocortin type 1 receptor (MC-1R) controls hair color by balancing the synthesis of eumelanin and pheomelanin, influencing the pigmentation of hair follicles.
Describe the process of pheomelanin synthesis and its regulation.
Pheomelanin synthesis occurs when MC-1R signaling is inhibited by Agouti signal protein (ASP), which competes with α-MSH for binding to MC-1R. ASP expression is positively regulated by BMP signaling, and although ASP is expressed in human skin, its role in human pigmentation remains unclear.
What are the effects of aging on melanocyte activity in hair follicles?
Aging leads to premature loss and graying of hair, characterized by fewer melanocytes in the bulb of gray hair. Inactive melanocytes and stem cells in the outer root sheath are markedly reduced in gray hairs, and melanocyte stem cells are damaged, affecting their ability to produce pigment.
How do α-MSH and ACTH influence melanocyte behavior?
α-MSH and ACTH, which bind to MC-1R expressed by hair follicle melanocytes, promote melanocyte proliferation, dendricity, and pigment production, enhancing the overall pigmentation process.
What is the role of β-endorphin in melanocyte function?
β-endorphin promotes melanocyte proliferation, dendricity, and pigment production by binding to the μ-opiate receptor and modulating the activity of protein kinase C, which is a positive regulator of pigment production.
What happens to melanogenic activity during the catagen phase of hair follicle development?
During the catagen phase, melanogenic activity in follicular melanocytes ceases, with some pigment-producing melanocytes undergoing apoptosis and others dropping into the dermal papilla of the follicle.
What are the essential co-factors for melanogenic enzymes?
Essential co-factors for melanogenic enzymes include 6-tetrahydrobiopterin, which is necessary for the activity of enzymes like tyrosinase, tyrosinase-related proteins, glutamyltranspeptidase, and peroxidase.
How does ATM-kinase contribute to melanocyte stem cell function in the context of aging?
ATM-kinase acts as a central transducer of the DNA-damage response, protecting melanocyte stem cells from premature differentiation, which is crucial for maintaining melanocyte populations as hair grays with age.
What is the significance of the bulge area in hair follicle anatomy?
The bulge area is significant because it contains stem cells that are crucial for hair follicle regeneration and repair. It plays a key role in the hair cycle, particularly during the anagen phase, where hair growth occurs.
What are the key stages of hair follicle morphogenesis and their associated molecular regulators?
The key stages of hair follicle morphogenesis include: 1. Stage 1: Hair placode formation - Involves BMP, EDA, and DKK. 2. Stage 2: Hair bud formation - Involves SHH, PDGF, and neurotrophins. 3. Stage 3: Hair peg formation - Involves CK5 and CK14. 4. Stage 4: Differentiation of inner root sheath - Involves CK10 and Loricrin. 5. Stage 5: Differentiation of hair shaft - Involves Hair keratins and Notch signaling. 6. Stage 6: Formation of sebaceous glands - Involves BMP and Wnt signaling. 7. Stage 7: Bulge formation - Involves TGF-β and BMP signaling. 8. Stage 8: Hair cycle initiation - Involves various growth factors and signaling pathways.
How do the signaling pathways influence the differentiation of hair follicle structures?
Signaling pathways play a crucial role in the differentiation of hair follicle structures by: - SHH (Sonic Hedgehog): Promotes hair follicle development and growth. - BMP (Bone Morphogenetic Proteins): Regulates the transition between different stages of hair follicle development. - Wnt signaling: Influences the proliferation and differentiation of hair follicle cells. - Notch signaling: Affects the fate of progenitor cells in the hair follicle. - PDGF (Platelet-Derived Growth Factor): Supports the growth and survival of dermal papilla cells.
What is the significance of the bulge area in hair follicle anatomy?
The bulge area is significant in hair follicle anatomy because it: - Serves as a reservoir of stem cells that can regenerate the hair follicle during the hair cycle. - Plays a role in the initiation of hair growth during the anagen phase. - Contains dermal papilla cells that interact with the hair matrix to regulate hair growth and cycling. - Is involved in the response to hormonal signals that influence hair follicle activity.
Describe the phases of the hair cycle and their characteristics.
The phases of the hair cycle include: 1. Anagen: Active growth phase where the hair follicle is deeply anchored in the dermis. 2. Catagen: Transitional phase where hair growth slows and the follicle shrinks. 3. Telogen: Resting phase where the hair is shed and the follicle remains inactive until the next anagen phase. 4. Exogen: Shedding phase where old hair is released, making way for new hair growth.
What role do neurotrophic factors play in hair follicle innervation?
Neurotrophic factors play a critical role in hair follicle innervation by: - Supporting the survival and growth of nerve fibers that innervate the hair follicle. - Regulating the interaction between neurons and hair follicle cells, influencing hair growth and cycling. - Modulating the response of hair follicles to external stimuli, such as touch or temperature changes. - Contributing to the maintenance of hair follicle homeostasis and function.
What are the different types of hair and their characteristics based on anagen duration and size?
Type of Hair | Anagen Duration | Size (Diameter, Length) |
|————–|—————–|————————-|
| Lanugo | 1-3 months | 40 µm, 1-2 cm |
| Vellus | 1-2 weeks | <30 µm, <2 cm |
| Terminal | >1 year | >60 µm, 10-100 cm |
| Miniaturized | >1 year | <30 µm, <2 cm |
How do bulge-derived and non-bulge-derived cells contribute to epidermal renewal after wounding?
- Bulge-derived cells:
- Contribute to the epidermis for immediate wound closure.
- Required for hair follicle cycling.
- Diminish over time after wounding.
- Non-bulge-derived cells:
- Predominate in the reepithelialized area over time.
- Involved in the later stages of wound healing.
What is the relationship between epidermal and hair follicle stem cells during homeostasis and after wounding?
- During homeostasis, epidermal renewal relies on cell proliferation within the epidermis.
- After wounding:
- Immediate closure: Bulge cells contribute to the epidermis for quick wound closure.
- Anagen onset: Bulge-derived cells are essential for hair follicle cycling.
- Long-term healing: Non-bulge-derived cells become more prominent in the reepithelialized area over time.
What are the characteristics of the different types of hair based on their anagen duration, size, and type?
Type of Hair | Anagen Duration | Size (Diameter, Length) |
|————–|—————-|————————-|
| Lanugo | 1-3 months | 40 µm, 1-2 cm |
| Vellus | 1-2 weeks | <30 µm, <2 cm |
| Terminal | >1 year | >60 µm, 10-100 cm |
| Miniaturized | >1 year | <30 µm, <2 cm |
How do bulge-derived and non-bulge-derived epithelial stem cells differ in their roles during wound healing?
- Bulge-derived stem cells:
- Contribute to immediate wound closure after injury.
- Required for hair follicle cycling.
- Diminish over time post-wounding.
- Non-bulge-derived stem cells:
- Predominate in the re-epithelialized area after a period of healing.
- Involved in long-term epidermal renewal post-injury.
What is the significance of the relationship between epidermal and hair follicle stem cells during homeostasis?
During homeostasis, epidermal renewal relies on cell proliferation within the epidermis.
What are bulge-derived stem cells?
Bulge-derived stem cells contribute to immediate wound closure after injury, are required for hair follicle cycling, and diminish over time post-wounding.
What are non-bulge-derived stem cells?
Non-bulge-derived stem cells predominate in the re-epithelialized area after a period of healing and are involved in long-term epidermal renewal post-injury.
What is the significance of the relationship between epidermal and hair follicle stem cells during homeostasis?
During homeostasis, epidermal renewal relies on cell proliferation within the epidermis, while hair follicle bulge stem cells do not contribute to this process.
What changes occur in the role of bulge-derived stem cells after full-thickness wounding?
After full-thickness wounding, bulge-derived stem cells contribute to the epidermis for immediate wound closure, initiate the anagen phase of hair follicle cycling, and their presence diminishes over time.
How does the expression of keratin genes vary in different compartments of hair follicles?
The expression of keratin genes varies by compartment:
- Outer root sheath: K14, K15, K17
- Inner root sheath: K25, K27, K31
- Hair matrix: K31, K35
- Hair medulla: K41, K43, K81.
What is the clinical significance of understanding the relationship between hair follicle stem cells and wound healing?
Understanding this relationship is crucial for developing targeted therapies for skin injuries and hair loss, enhancing wound healing processes, and improving regenerative medicine approaches.
What are the implications of the findings regarding hair types and their characteristics for clinical practice?
The implications include tailoring hair restoration treatments based on hair type characteristics, understanding patient-specific hair growth patterns, and informing cosmetic and dermatological procedures.
How does the duration of the anagen phase differ among various hair types?
The duration of the anagen phase varies:
- Lanugo: 1-3 months
- Vellus: 1-2 weeks
- Terminal: >1 year
- Miniaturized: >1 year.
What role do epithelial stem cells play in the re-epithelialization process after wounding?
Epithelial stem cells facilitate immediate wound closure through proliferation and migration, contribute to the restoration of the epidermal barrier, and ensure long-term maintenance and regeneration of the epidermis.
What factors influence the transition from bulge-derived to non-bulge-derived stem cells during the healing process?
Factors influencing this transition include time post-wounding, environmental signals, and cellular interactions.
What are the distinct subpopulations of melanocytes present during the hair cycle?
The distinct subpopulations of melanocytes include:
- Telogen: Melanocyte stem cell (Trp2+/Ki67-c-kit+)
- Early Anagen: Undifferentiated melanocytes (Trp2+/Ki67+c-kit+)
- Mid-Anagen: Undifferentiated melanocytes (Trp2+/Trp1+; Ki67-c-kit+)
- Late Anagen: Differentiated melanocytes (Trp2+/Trp1+; Ty+; Ki67-c-kit+; MC-1R+).
What is the significance of distinct subpopulations of melanocytes in hair pigmentation?
These subpopulations are crucial for the cyclic regeneration of the hair pigmentation unit, influencing hair color and growth.
How does the expression of melanin markers and growth factor receptors change during the hair cycle?
During the anagen phase, melanocytes transition from undifferentiated states in early and mid-anagen to differentiated states in late anagen, essential for hair pigmentation.
What role does SCF/c-Kit signaling play in the hair cycle?
SCF/c-Kit signaling is essential for the maintenance and proliferation of melanocyte stem cells and their differentiation during the anagen phase.
What are the implications of the presence of differentiated melanocytes in the late anagen phase for hair pigmentation?
The presence of differentiated melanocytes indicates active melanin production, contributing to hair pigmentation and establishing hair color.
How do the characteristics of melanocytes change from the telogen phase to the late anagen phase?
In the telogen phase, melanocyte stem cells are quiescent, while in the late anagen phase, melanocytes are differentiated and actively producing melanin.
Primary purpose of hair in humans?
Influence social interactions
The first hairs formed are _____, which are nonpigmented, soft, and fine. They are typically shed between the _____ weeks of gestation, although
approximately one third of newborns still retain them for up to several weeks after birth.
lanugo hairs
32nd and 36th
_____, a type of homeobox gene, is responsible for dorsal-ventral patterning, and mice lacking this develop hair follicles on their footpads.
Engrailed
Anagen duration, diameter and size of lanugo hair?
Anagen duration, diameter and size of vellus hair?
Anagen duration, diameter and size of terminal hair?
Anagen duration, diameter and size of miniaturized hair?
Describe the stages of the hair follicle cycle.
Enumerate the anatomical layers of the hair from outer to innermost.
Type 1 and 2 keratin genes in the outer root sheath?
Type 1 and 2 keratin genes in the companion layer?
Type 1 and 2 keratin genes in the hair matrix / precortex?
Type 1 and 2 keratin genes in the Henle layer?
Type 1 and 2 keratin genes in the Huxley layer?
Type 1 and 2 keratin genes in the IRS cuticle?
Type 1 and 2 keratin genes in the hair cuticle?
Type 1 and 2 keratin genes in the mid-and upper hair cortex?
Type 1 and 2 keratin genes in the hair medulla?
Autosomal dominant mutations of K81 and K86 lead to _____.
Monilethrix
Constant activation of WNT/B catenin signaling results to _____ and _____.
Pilomatricomas
Trichofolliculomas
EDA mutation results to?
X-linked anhidrotic ectodermal dysplasia
EDAR mutation results to?
Hypohidrotic ectodermal dysplasia
Responsible for length of hair?
FGF-5
Responsible for curl of hair?
K71
Responsible for distribution of hair?
R-spondin 2
Responsible for thicker hair in Asians?
EDAR
Signaling family that inhibits hair follicle/placode formation?
BMP
Antagonist of BMP that promotes placode fate through increased Lef-1?
Noggin
Responsible for follicular pattern, whose ligand is delta-1?
Notch pathway
Hair placode / hair germ 1st appears at ___ weeks AOG.
10
This is the receptor for SHH and is expressed in germ cells and underlying dermal papilla.
Patched1 (PTCH1)
This receptor is deficient in BCNS.
PTCH1
The matrix of the hair follicle gives rise to _____ and _____.
Hair shaft
Inner root sheath
Terminal hairs that are present at brith are found in the (3).
Scalp
Eyebrows
Eyelashes
The shape of the _____ determines the shape of hair.
Inner root sheath
Mutation in _____ and _____ results in curly hair.
EGFR
IGFBP5
The outer root sheath in the _____ has a granular layer and in the _____, it does not have it.
Infundibulum
Isthmus
Keratinocytes in the ORS for a bulb at the base of the isthmus characterized by?
Cells with increased nucleus to cytoplasmic ratio
Moving downward, the outer root sheath cells become much larger and
contain abundant _____ in the suprabulbar follicle. In the bulb, the outer root sheath consists of _____ that can be traced to the base of the follicle.
glycogen
only a single, flattened cell layer
The inner root sheath extends from _____ to the _____.
Base of the bulb
Isthmus
This layer attaches to the Henle layer and moves upward with the rest of the inner root sheath; thus, it provides a slippage plane between the outer
root sheath, which is stationary, and the inner root sheath. It is prominent in the beard and is composed of flat cells and expresses K6hf.
Companion layer
This layer is one cell layer
thick and is the first to develop keratohyalin granules and the first to keratinize.
Henle layer
This layer is two to four cell layers thick and keratinizes above the Henle layer at the region known as Adamson fringe.
Huxley layer
Some cells within the Huxley layer protrude through the Henle layer and attach directly to the companion layer. These cells are called _____.
Fluegelzellen or wing cells
The cells of the _____ partially overlap, forming a “shingled roof” appearance, and they intertwine precisely with
the _____. This association anchors the hair shaft tightly to the follicle.
inner root sheath cuticle
cuticle cells of the hair shaft
The transcription factor _____ is critical for inner root sheath differentiation and lineage. Mice lacking this gene fail to form an inner root sheath.
GATA-3
Differentiation of hair shaft cells in the prekeratogenous is dependent on this transcription factor.
Lef-1
The hair shaft (and inner root sheath) arises from rapidly proliferating _____, which have one of the highest rates of proliferation in the body.
matrix keratinocytes in the bulb
_____ is also critical for matrix cell
differentiation into the hair shaft because loss of this receptor prevents hair shaft differentiation.
BMP receptor type 1a
The _____ comprises the bulk of the shaft and contains melanin. It is arranged in large cable-like structures called macrofibrils. These, in turn, possess microfibrils that are composed of intermediate filaments.
cortex
The _____ sits at the center of larger hairs, and specific keratins expressed in this layer of cells are under the control of androgens.
medulla
The _____ is a core of mesenchymally derived tissue enveloped by the matrix epithelium. It is comprised of fibroblasts, collagen bundles, a mucopolysaccharide-rich stroma, nerve fibers, and a single capillary loop. It is continuous with the perifol-
licular sheath (dermal sheath) of connective tissue that envelops the lower follicle.
dermal papilla
T or F: In human follicles, the volume of the dermal papilla correlates with the number of matrix cells and the resulting size of the hair shaft.
True
_____ is produced by the anagen dermal papilla, and its receptor, _____, is found predominantly in the matrix keratinocytes. Injections of this growth factor into nude mice produce striking hair growth at the site of injection, suggesting that it is perhaps necessary for hair growth and cycling.
keratinocyte growth factor (KGF)
FGF receptor 2 (FGFR2)
_____ run parallel to hair
follicles, surrounding them and forming a network. Smaller nerve fibers form an outer circular layer, which is concentrated around the _____ and the _____.
Myelinated sensory nerve fibers
bulge of terminal follicles
bulb of vellus follicles
_____ transmit pain.
Free nerve endings
_____ detect acceleration.
Lanceolate nerve endings
_____ sense pressure.
Merkel cells
_____ detect tension.
pilo-Ruffini corpuscles
Perifollicular nerves contain neuromediators and neuropeptides, such as _____ and _____, that influence follicular keratinocytes and alter hair follicle cycling.
substance P
calcitonin gene-related peptide
In addition to neuropeptides, nerve fibers innervating hair follicles produce _____ that signals to a population of cells in the bulge marked by Gli1. The progeny of responding perineural bulge cells incorporate into healing skin wounds where, notably, they can change their lineage into epidermal stem cells.
Shh
Merkel cells are concentrated in the___ area, thus some have postulated that these secreted factors may influence the cycling of the hair follicle.
bulge
The basement membrane of the follicle is most prominent around the _____ in anagen hairs. During
catagen, the basement membrane thickens and then disintegrates.
outer root sheath at the bulb
The perifollicular sheath envelops the epithelial components of the hair follicle and consists of an inner basement membrane called the _____ and an outer _____ composed of type ___ collagen.
hyaline or vitreous (glassy) membrane
connective tissue sheath
3
Each individual hair follicle perpetually traverses through three stages: (1) growth (_____), (2) involution (_____), and (3) rest (_____). The length of _____
determines the final length of the hair and thus varies according to body site; the other 2 stages’ duration vary to a lesser extent depending on site.
anagen
catagen
telogen
anagen
Scalp hair has the longest anagen of _____.
2 years to more than 8 years
Anagen duration in young males at other sites is shorter:
legs, _____;
arms, _____;
eyelashes, _____; and
fngers, _____.
5 to 7 months
1.5 to 3.0 months
1 to 6 months
1 to 3 months
Approximately _____% of
scalp follicles are in anagen, and the rest are primarily in _____.
90% to 93%
telogen
How many hairs are on the scalp?
100,000 to 150,000 hairs
How many hairs do adults lose per day?
50 to 100 hairs per day
The follicles that are shedding
their hair shafts are thus in “_____,” which comprises approximately ___% of the telogen hair follicles.
exogen
1%
Hair on the scalp grows at a rate of _____ mm/day or approximately ___ cm/month.
0.37 to 0.44
1
Loss of hair follicle stem cells in the bulge leads to _____.
permanent or cicatricial types of alopecia
Markers that have been shown through genetic lineage analysis to contribute to the perpetual cycling of the hair follicle include
_____ and _____.
cytokeratin 15, Lgr5
_____, although sometimes touted as an exclusive marker of secondary germ cells, also marks bulge cells.
Lgr5
_____, a gene related to Lgr5, is expressed in an area above the bulge in the upper isthmus. The cells marked by this gene migrate to the epidermis during homeostasis and after wounding.
Lgr6
Bulge cells do not normally move to the epidermis, but after full-thickness excision of the skin, bulge cell progeny migrate into the wound during reepithelialization. These cells comprise approximately ___% of the cells in the regenerated epidermis.
30%
Enumerate the 7 stages of anagen.
1—growth of the dermal papilla and onset of mitotic activity in the germlike overlying epithelium
2—bulb matrix cells envelop the dermal papilla and begin differentiation, and the evolving bulb begins descent along the fibrous streamer
3—bulb matrix cells show differentiation into all follicular components
4—matrix melanocytes reactivate
5—hair shaft emerges and dislodges telogen hair
6—new hair shaft emerges from skin
surface
7—stable growth.
The onset of ____ is marked by cessation of the mitotic activity of the matrix cells and by well-coordinated apoptosis in the cyclic portion of the hair follicle.
catagen
The formation of a new lower follicle and hair at _____ onset recapitulates folliculogenesis in the fetus.
anagen
The migration of the dermal papilla from the subcutaneous fat to the dermis during catagen is necessary for continued follicle cycling. This is illustrated by the syndrome of _____. These patients have mutations in either their _____ or in their _____, in which case they also have _____. Although bulge cells are still present, no new anagen follicles ever form, presumably because the stem cells cannot interact with the dermal papilla.
atrichia with papules
hairless gene
vitamin D receptor gene, rickets
Mice lacking the _____ gene have hair that is 50% longer than their wild-type littermates and that mutations in this gene are responsible for the angora phenotype.
Fgf5 gene
Expression of this gene was upregulated in the outer root sheath and hair matrix cells just before the onset of catagen, suggesting that it may trigger catagen onset.
Fgf5 gene
The hair phenotype of FGF-5–deficient mice is substantially reversed
by ectopic expression of the antiapoptotic gene in the outer root sheath, suggesting that regulation of cell survival in the outer root sheath may play a role in control of the hair growth cycle.
bcl-xL
Knockout mice lacking _____, the major
ligand for EGFR, have abnormal hair follicle development and manifest the waved hair phenotype.
TGF-α
Signals that induce premature catagen (4):
FGF5
EGF
Neurotrophins
TGF-B1
___% of telogen hairs are shed each day.
1%
Exogen is an active stage is supported by Headington’s description of one type of telogen effluvium he termed
_____. This type of hair loss can be
seen soon after starting medications, such as minoxidil, or in response to rapid fluctuations in light–dark cycles.
It consists of an increase in shedding of club hairs within weeks of the precipitating event (too soon to be caused by follicles prematurely entering telogen from anagen),
suggesting that club hairs that are normally retained in the follicle can be actively shed.
immediate telogen release
Hair pigmentation is strictly coupled to ______ stage.
anagen
Melanoblasts can be identified in the epidermis of human embryos at ___ days EGA.
50
Melanocytes in the skin arise from two
sources: from _____ and from _____.
Neural crest cells migrating in the dorsolateral pathway
Schwann cell progenitors located in cutaneous nerves
Commitment of neural crest cells to the melanocyte lineage is regulated
by _____ and _____, which stimulate the expression of _____, an
enzyme involved in melanin biosynthesis that also
functions as an early melanoblast marker.
Pax3, microphthalmia transcription factors (Mitf)
dopachrome tautomerase (or tyrosinase-related protein 2131)
Subsequent steps of melanoblast development (migration into the dermis and epidermis) are controlled by signaling mechanisms activated through _____ and _____, which are
mutated in humans with _____ and _____, respectively, resulting in formation of unpigmented hairs.
endothelin receptor type B (Ednrb)
c-kit receptor
Hirschsprung disease
piebaldism
Melanocyte stem cells can be first detected in the _____ during _____ and similar to epithelial stem cells they
are quiescent.
bulge area
late stages of hair follicle morphogenesis
_____ signaling plays an important role in controlling melanocyte stem cells entering into a noncycling (dormant) state during hair follicle morphogenesis.
TGF-β
_____ signaling plays a crucial role
in the survival of melanocyte stem cells and immature melanoblasts by preventing apoptosis.
Notch
_____ plays a key role in maintenance of melanocyte stem cells.
Bcl2
Melanocytes producing pigment are located in the _____.
hair bulb above the dermal papilla
Melanocytes express a full set of enzymes and other proteins involved in melanin biosynthesis including _____, _____, and _____. Keratinocytes, as pigment recipient cells, produce _____ and its target _____ to identify themselves as the targets for pigment transfer.
tyrosinase
Trp1
pMel17
Foxn1
Fgf2
Some of HF melanocytes in telogen also express c-kit receptor, and others remain c-kit-negative and represent _____.
_____ in MCSCs drives their wqqr54radifferentiation into pigment-producing melanocytes.
melanocyte stem cells (MCSCs)
Wnt activation
Hair follicle melanocytes are maximally proliferative during early and midanagen, and their transition to melanogenic competence is accompanied by the appearance of _____ and _____.
Trp1
tyrosinase protein
_____ signaling is necessary to prevent differentiation of melanoblasts into pigment-producing melanocytes
before they reach the hair bulb, as well as for their proper positioning in the hair matrix.
Notch
_____/_____ signaling plays a critical role in repopulation of the bulb with pigment-producing melanocytes.
SCF
c-kit
MC-1R is expressed by hair follicle melanocytes, and its ligands _____ and _____ are able to promote melanocyte
proliferation, dendricity, and pigment production.
α-MSH
adrenocorticotrophic hormone (ACTH)
The balance between black and yellow pigment synthesis (eumelanin and pheomelanin, respectively) is regulated by signaling through
the _____ that has long been implicated in the controlling hair color.
melanocortin type 1 receptor (MC-1R)
Follicular melanocytes are sensitive to aging, which results in their premature loss and hair greying. State some of these changes on a cellular level.
- Fewer melanocytes are found in the bulb of a grey hair
- Inactive melanocytes (melanoblasts including stem cells) in the outer root sheath are markedly reduced in follicles producing grey hairs
