Chapter 4: Developmental Biology of the Skin

Question 1

____________________ are immune cells that reside predominantly in the epidermis, and internalize and present potentially harmful antigens encountered in the environment to initiate an immune response.

Answer 1

Langerhans cells

Question 2

___ is a transcription factor with multiple isoforms that is perhaps the central regulator of epithelial identity.

Answer 2

p63

Question 3

____ is very important to hair follicle formation and function.

Answer 3

Shh

Question 4

______

It is critically important for the development of appendages

Answer 4

EDAR (ectodysplasin A receptor)

Question 5

BMP (bone morphogenic protein) ligands are a family of ligands that bind BMP receptors and, among other functions, regulate _______________

Answer 5

hair follicle cycling and growth

Question 6

____________ transcription factor family is important in large-scale body patterning

Answer 6

HOX (homeobox)

Question 7

The cell that composes the majority of the epidermis is the ___________, so named because the structural protein keratin is abundant in that cell

Answer 7

keratinocyte

Question 8

While keratins are the protein most abundant in the epidermis, _________ are the most abundant protein in the dermis.

Answer 8

collagens

Question 9

The primary cell of the dermis is the _________, which produces collagens but has a large repertoire of other functions

Answer 9

fibroblast

Question 10

The third trimester runs from weeks ________ and is when most development completes, including the formation of the _________ from the skin whose function is thought to lubricate for the pas- sage through the birth canal

Answer 10

26 to 40

vernix caseosa

Question 11

The morula divides to form a more complicated structure called a ______, which has 2 main parts

1) ______
2) ______

Answer 11

blastula
trophoblast (placenta)
inner cell mass (embryo)

Question 12

The _________ forms eventually the epidermis and melanocytes, but also the nervous system

Answer 12

ectoderm

Question 13

Neural crest development initiates during the _______ of fetal life when the ectoderm forms the neural plate within it

Answer 13

third week

Question 14

Although they mostly contribute to the axial skeleton and muscles, early somite fibroblasts are also precursors for ___________

Many of these fibroblasts—especially from body locations such as the back—originate from the dorsolateral portions of the somite, which is also called the _______________.

Answer 14

dermal fibroblasts

dermatomyotome

Question 15

Non–melanocyte-related diseases of neural crest migration include _________________________ where 22q11.2 deletion results in defects in cardiac, craniofacial, and endocrine organs, among others.1

Answer 15

DiGeorge syndrome

Question 16

Skin forming begins when the ectoderm converts to a single layer known as the _____________—a cuboidal, mitotically active and undifferentiated layer.
It expresses the gene _____, which is vital for epidermal differentiation and also corrupted in the EEC syndrome.

Answer 16

germinativum

p63

Question 17

Genes that control periderm formation include _____, _____, and IKKα, likely partially through the nuclear factor kappa B (NF-κB) pathway.

Recent evidence suggests it is also a protective layer that prevents pathologic adhesions to adjacent epithelium, so that lack of periderm formation leads to the _________________

Answer 17

SFN, IRF6

human cocoon syndrome

Question 18

The dermis is formed from the mesodermal layer of the embryo; consequently, it is referred to as ___________

Answer 18

mesenchyme

Question 19

Whereas fibroblasts from the ventral body are thought to derive from _______________, fibroblasts from the head are thought to develop more from ____________________, and those, for example, of back skin are more likely to develop from _________ (and more specifically dermatomyotomes).

Answer 19

lateral plate mesoderm
neural crest precursors
somites

Question 20

In particular, fibroblasts are programmed with a specific combination of ________, which, even after culturing of fibroblasts, are retained to specify,

Answer 20

HOX genes

Question 21

The upper dermal fibroblast progenitor (PDGFRa+, _______, Dlk−, ____) become dermal papillae (a ball of fibroblasts that control hair keratinocytes), arrector pili muscle (muscle attached to hair that causes goosebumps), and the fibroblast of the upper dermis termed ______________.

Answer 21

Blimp1+
Irig1+
papillary fibroblasts

Question 22

The lower dermal fibroblast progenitor (PDGFRa+, Blimp1−, Dlk1+) give rise to not only adipocytes but to the _________ (lower density and biased _______ over col- lagen III production).

Answer 22

reticular fibroblasts

collagen I

Question 23

Even though peroxisome- proliferator-activated receptor γ (PPARγ) is an important transcription factor for both white and brown adipose development, ______ appears to be uniquely important for brown adipose development

Answer 23

Prdm16

Question 24

Hallmark clinical syndromes of defects in mesenchymal development include focal dermal hypoplasia or ________ caused by mutations in the PORC gene,

Answer 24

Goltz syndrome

Question 25

Analogous clinical syndromes for adipose tissue include the lipodystrophy syndromes such as Berardinelli-Seip where a lack of adipose development occurs from defects in the lipid synthesizing ________

Answer 25

AGPAT2 gene

Question 26

Melanocytes can be detected by the _________ estimated gestational age (EGA) in human epidermis

Answer 26

eighth week

Question 27

Their (melanocyte) precursor is a __________ progenitor, which also can differentiate into glial cells in addition to melanocytes.

Answer 27

SOX10-positive

Question 28

These precursor cells actually can lose expression of MITF and KIT to revert to a ___________—the adult melanocyte stem cells—that live in the _________ bulge stem cell compartment

Answer 28

melanoblast

hair follicle

Question 29

In addition to populating hair follicles, melanoblasts are thought to home to sweat glands where they might contribute to ___________.
These melanocyte stem cells supply interfollicular melanocytes as well, most dramatically during ultraviolet light therapy for patients with ________

Answer 29

acral melanomas

vitiligo

Question 30

dermal melanocytes are thought to persist after birth in several locations, including the dorsa of the hands and feet, the _________, and the scalp. These areas are clinically important because they are also common sites for ________.

Answer 30

sacrum/buttocks

blue nevi

Question 31

Another example of defective melanocyte development is piebaldism where disrupted melanocyte _________ secondary to defects in, for example, __________ signaling lead to areas of albinism

Answer 31

migration

c-kit growth factor

Question 32

In the skin, sensory neurons develop from the ________ (head) or __________ (elsewhere)

Answer 32

trigeminal

dorsal root ganglia

Question 33

Merkel cells are found as early as ________ EGA with particular high density at volar sites, appendages, and ________

Answer 33

12 weeks

nerves

Question 34

The earliest morphologic changes are the formation of a hair placode in the epidermis, where the keratinocytes become thinner, columnar, and tightly packed. This occurs around ___________

Answer 34

75 days EGA

Question 35

The following stage is the hair germ phase (___________; sometimes referred to as hair bud), which is the more pronounced downward movement of epithelium forming a ___________, followed by continued downward epithelial invasion through the peg stage (100 days EGA).
During the peg stage, the epithelium begins to wrap around and encompass the associated inductive fibroblast population, which is now called the _______________

Answer 35

80 days EGA
clear nubbin
dermal papillae

Question 36

The activity of ________ is perhaps the most important for appendage development

Answer 36

β-catenin

Question 37

Downstream genes that are activated and necessary for morphogenesis include the ________ and ________ functions.

Answer 37

ectodysplasin ligand (EDA) and receptor (EDAR)

Question 38

Sebaceous glands develop during the bulbous peg phase from _____ ______ hair follicle keratinocyte stem cells during 13th to 14th weeks of fetal life.

Answer 38

SOX9+ LRIG1+

**Interestingly, while sebaceous glands have a dip in activity during childhood, they are more active during embryogenesis (in the production of the vernix caseosa) and puberty

Question 39

Nail development also requires HOX programming as is evident by patients with nail-patella with mutations in the __________.

Answer 39

HOX gene LMX1b.

Question 40

Volar dermatoglyphics development begins around ______ EGA when protuberances in palms and soles, called volar pads, appear

Answer 40

week 7

Question 41

(Vascular)
Following this, they arborize and sprout to extend themselves to mature in reactions involving ________ and _________.
__________ is required for the recruitment of associated cells such as pericytes

Answer 41

TGF-β and platelet-derived growth factor (PDGF)

Angiopoietin-1

Question 42

While the EphrinB2 released by arteries as a ligand for ______ receptor on veins is important to maintain the arteriovenous (A-V) plexus, how arteries and veins are juxtaposed has only recently been elucidated.

In one current model, the signaling agent ______ is produced from arterial endothelial cells, and stimulates chemotaxis and expression of _____, a G-protein–coupled receptor, on venous endothelial cells to promote A-V alignment.

Answer 42

EphB4

Apelin
APJ

Question 43

Lymphatic development occurs through the maturation of established venous endothelial cells that express ______.
These cells bud and migrate off to establish lymph vessels, first in regions of _______ expression in the _____________.

Answer 43

PROX1
VEGF-C
lateral mesoderm

Question 44

One hallmark disease is the Sturge-Weber syndrome where defects in the gene _______ cause prominent port-wine stains on the ______, as well as __________ anomalies leading to seizures and mental retardation, among other symptoms, and which is more concerning than the port-wine stains

Answer 44

GNAQ
face
intracranial vascula

Question 45

The yolk sac also generates some important myeloid lineages, such as the skin-specific antigen presenting cells known as the Langerhans cell –> are detectable by ________ of gestation.

The second wave of development of hematopoietic cells occurs in the ________, with later contributions from the liver

Answer 45

10 weeks

dorsal aorta

Question 46

hyperimmunoglobulin E (hyper-IgE) syndrome or Job syndrome where _________________ mutations—a vital signaling molecule in lymphocytes—leads to impaired T-helper cell 17 (TH17) development and, instead, to excessive ___________ profile of eosinophilia and hyper-IgE characterized by chronic eczema and recurrent skin Staphylococcus aureus infections

Answer 46

signal transducer and activator of transcription 3 (STAT3)

T-helper cell 2 (TH2)