Adnexal Units (including diseases) Flashcards
Structure and function of the hair follicle, sebaceous gland, and sweat glands with important associated diseases.
What are the functions of hair?
- Thermoregulation (dependent on length, thickness, density, medulation, piloerection, and gloss)
- Physical protection (UV, chemical, physical, microbial)
- Social interactions (scent, piloerection, color)
- Camouflage
- Stem cells for wound healing
- Dispersing sweat/sebum
Most hair follicles develop before birth, which do not?
- All hair in marsupials
- Secondary follicles in dogs
Which tissues in the hair follicle are ectodermally derived?
- All epithelial components
- Sebaceous glands
- Apocrine glands
Which tissues in the hair follicle are mesodermally derived?
- Hair papilla
- Connective tissue sheath
Which tissues in the hair follicle are neural crest derived?
Melanocytes
Describe where hair first appears on the embryo.
Vibrisse on the chin, eyebrow, and upper lip for first then hair begins to form all over the head and then moves down
What are lanugo hairs?
- First hairs formed in utero
- Non-medulated
- Typically shed in humans before birth
What genes are likely responsible for non-random placement of hair?
- Homeobox genes
- Mice with Engrailed knockout get hair on paw pads
How many stages are there in hair follicle development?
8
(7 in anagen, 8 in catagen)
What happens to the genes and signaling molecules that are involved in the development of the hair follicle when the individual becomes an adult?
Most of the become involved in hair cycling.
What happens first in the development of the hair follicle (stage 1 aka hair placode stage)?
- An epithelial placode/hair placode/hair germ begins to form in the epidermis (goes on to form the entire epithelial portion) due to the influence of Wnt/β-catenin, EDA/EDAR, BMP, noggin, and follistatin
- Then the mesenchymal/dermal condensate forms underneath (goes on to form the dermal papilla) under the influence of Wnt, PDGF, and Shh
What happens second in the development of the hair follicle (stage 2 aka hair peg stage)
Epithelial placode proliferates, invades the dermis, and surrounds the dermal condensate largely mediated by Shh
(later stages will go on to differentiate into inner and outer root sheath and form bulges)
The outer root sheath of the hair peg goes on to form 3 bulges. What does the deepest bulge form?
The arrector pili attachment
The outer root sheath of the hair peg goes on to form 3 bulges. What does the middle bulge form?
Sebaceous gland
The outer root sheath of the hair peg goes on to form 3 bulges. What does the most superficial bulge form?
Sweat gland
What does the fibroblast growth factor 5 (FGF-5) gene do during hair follicle development?
- Responsible for hair length
- Is a catagen inducer in the mature follicle (so abnormalities lead to longer hair)
What does the keratin-71 gene do during hair follicle development?
Is responsible for hair curl
What does the R-spondin 2 gene dictate about hair?
Hair size and texture (and distribution)
What does the Wnt/β-catenin pathway do during hair development?
-“master switch”
- required for hair follicle induction and initial placode development
- originates from epidermal cells
- determines differentiation into hair follicle keratinocytes
- plays an important role in regulating expression of hair shaft keratin genes as nearly all of them have Lef-1 binding sites in their promoter region
- β-catenin is the downstream mediator of Wnt signaling
- once activated β-catenin translocates to the nucleus and interacts with the LEF/TCF family of genes (Lef-1) which then impact downstream genes including homeobox genes
- these are normally inactive (except for inducing anagen) in the adult epidermis but constant activation results in pilomatricomas and trichofolliculomas
What does EDA/EDAR do during hair development?
- Part of another major pathway that stimulates early follicle development/promotes follicle development
- Is essential for the development of multiple ectodermal tissues (hair, teeth, glands) so mutations in this result in ectodermal dysplasias
- Is a downstream mediator of Wnt signaling
- Mice overexpressing this have fused follicles due to lack of proper spacing
What does BMP (bone morphogenetic protein) do during hair development?
- Works in contrast to EDA/EDAR by inhibiting hair follicle/placode formation
- Is essential for correct distribution of follicles and differentiation of inner root sheath/hair shaft
- Induces catagen in the mature follicle
- Its antagonist is Noggin
What does noggin do during hair development?
- Antagonizes BMP
- Promotes placode fate by increasing Lef-1 expression and works to induce anagen in the mature follicle
What does TGF-α/EGF do during hair development?
Induce catagen in the mature follicle
What does the Notch pathway do during hair development?
- Comes from the hair bulb and outer root sheath
- Not that important for embryonic development
- Important for post-natal development leading to differentiation into hair and the the development of the shat and inner root sheath
- Also appears to control the phenotype of keratinocytes as they leave the bulb matrix