Lecture 6 skin appendages Flashcards

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1
Q

what layers does the skin consist of

name some cell type

A

epidermis- a stratified squamous epithelium originating from the ectoderm composed primarily of keratinocytes;
dermis- a connective tissue whose principal cellular component the fibroblast is derived from mesoderm;
hypodermis or subcutaneous adipose layer comprising adipocytes, fibroblasts and macrophages
Merkel cells
melanocytes
sensory nerves (ncc)
dendritic cells
endothelial cells

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2
Q

what are appendages

A

protruding structures that augment the skins primary fucntions

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3
Q

what are placdes

A

characterisitc condensations of both mesenchymal and ectodermal derived cells which in/e vaginate
beginning of all appendages

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4
Q

what are the cell types and nature of the epidermis

A

outer layer- enucleated keratinocytes which are continuously shed
once every 4 weeks replaced

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5
Q

where are stem cells of the skin that replace the epidermis

A

basal layer of the epidermis and bulge of hair follicles

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6
Q

how do the tem cells in teh epidermis replace the keratinocytes

A

asym div them amplification and migrate away from the basal layer terminally differentiate
rate of production compensates rate of loss

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7
Q

what T is required for the development of the epidermis

A

p63

req for the stratification in the embryonic ectoderm and for epidermal stem cell specification

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8
Q

what does knockdown experiments of p63 with siRNA show

A

in control - see the thickening of the differentiated cells

in the treatment ni proliferation and differentation

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9
Q

what axis has been found to regulate the stem cell to TA cel transition

A

Rac1-Miz axis

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10
Q

describe the Rac1-Miz axis

A

Integrins a6b4 expr in basal layer act. Rac which acting through the protein kinase Pak inh c-myc (TF). = mainatin stem cell
But c-Myc can inh the expr of integrins a6b4 and potentially Rac = loss of stem cell identity = result in TA fate.

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11
Q

what roles does Wnt have in homeostaiss of stme cell fate

A

stem cell specification,
stem cell activation
terminal differentiation.

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12
Q

what is the notch activity expression in the cells of the skin

A

highest in the spinous cells (switch on Hes1)
lowest in teh basal cells and granular cells
(gradient highest in mid decr either side)

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13
Q

what is the role of notch elucidating from its expr pattern

A

regulate cell fate decision from Ta cell to spinous cell fate

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14
Q

mesenchymal and epithelial cells make up most organs

what two distinct role do both cell types normally have

A

speciailised cells normally epithelial

mesenchymal cells = supporting role and send inductive signals to the epithelium

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15
Q

wat are the steps of hari follicles development

A

placode formation

follicle maturation

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16
Q

when does placode formation occur

A

In mouse being E14.5
both layers thicken and the epi invag the mesenchyme
a morpho change

17
Q

what happens when epithelial and mesenchymal cells in culture seprated

A

survive but no follicle formation

18
Q

describe the hari follicle structure

A

dermal papillae =mesenchymal component of hf at the inner most end
dermal cells are near the DP remain prolif and through contact with the DP have distinct gene expr
matrix cells die = form shaft
outer rrot sheath - contact with the b.mbn
inner root sheath provides channel for emerging hair
matrix -makes keratin
bulge - source of stem cells
sebaceous gland at the top

19
Q

what cell type is the hair follicle consist of

A

most epithelial

but mesenchyme contribute to DP

20
Q

what does tes reversing the epithial layer on mesenchyme result in and what does this show

A

epithelial placodes disapera

the mesenchyme placodes remaai- mesenchyme controls the placode postion

21
Q

what is the signal from the mesenchyme thought to be for placode postioning and what some propeties of it

A

potentially a Wnt
B catenin ko or DKK1 tgics do not develop HF
overexpr b cat - ectopic HF
continuously produced

22
Q

what is thought to be the singal from the epithelia to the mesenchyme

A

TGF-B2
expr in the epithelium
can subsitute for the epithelium if remove in the formation of Dermal papillae
likely only expr for a short time

23
Q

summarise the signals for the formation of hair follicle

A

mesenchyme to epitheium = where an appendage will form
epitheia singals back to the mesenchyme - maintain placode (TGF-B)
M to epithelium form region correct appendage
Epidermis gives ID of the species

24
Q

what sort of positional information contols the pattern formation of hair spacing
(note - all cells capable of becoming Hf)

A

relative (removing pieces of ski does not affect = spaceing generated locally)
(note limb is absolute as if remove big effect on final ptype )

25
Q

what mechanism controls spcing of hari follicles

A

lateral inhibiton

26
Q

what evidence is there for BMP as the inh signal of hair spacing

A

ectopic expr - no hair

ko - lots of hair

27
Q

what has the role of DKK (Wnt inh) in hair spacing thought to be

A

similar effect to bmp
incr dkkk loss of hf
= imply wnt signal inv

28
Q

what experiments showed what controls the identity of the appendage

A

seperate and cross epi and mesenchyme from diff regions

shows that the mesenchyme provides the regional information

29
Q

give examples of regional signals for appendages

A

LEF1 - hair

Sweat glands characterised by BMP (ko - sweat glands dev)

30
Q

what gives the species specific information

A

the epithelium

31
Q

what experiments shown the role of the epithelium in species specific appendage formation

A

cross the mice and chicken mesenchyme and epithelium

is the epithelium identity the aappendage which is made

32
Q

what is HF development an example of

A

reciprocal interaction/signalling controlling the morphogenesis of a strucutre

33
Q

what are the stages of the hair cycle

A

growth (anagen)
regression (catagen)
rest (telogen).
shedding phase (exogen,)

34
Q

what is the length of the hair dependent on

A

length of anagen phase = proliferation and differentiation of matrix cells at the follicle base

35
Q

descire the transition from telogen to anagen

A

quiescent stem cells in the bulge region act to proliferate by signals (wnts, shh) released by mesenchymal cells in the dermal papilla. This recapitulates follicle induction during embryogenesis.

36
Q

what physically does the catagen stage do

A

bring the DP closer to the stem cells in the bulge

37
Q

what is required to maintain the HF for life

and how this utilised

A

the dp
kill - stop unwanted hair growth
implant - hair transplant

38
Q

what is the role of fgf5 in anagen

A

ends the anagen phase and promotes catagen

mut - longer anagen - longer hair