Lecture 6 skin appendages Flashcards

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
what mechanism controls spcing of hari follicles
lateral inhibiton
26
what evidence is there for BMP as the inh signal of hair spacing
ectopic expr - no hair | ko - lots of hair
27
what has the role of DKK (Wnt inh) in hair spacing thought to be
similar effect to bmp incr dkkk loss of hf = imply wnt signal inv
28
what experiments showed what controls the identity of the appendage
seperate and cross epi and mesenchyme from diff regions | shows that the mesenchyme provides the regional information
29
give examples of regional signals for appendages
LEF1 - hair | Sweat glands characterised by BMP (ko - sweat glands dev)
30
what gives the species specific information
the epithelium
31
what experiments shown the role of the epithelium in species specific appendage formation
cross the mice and chicken mesenchyme and epithelium | is the epithelium identity the aappendage which is made
32
what is HF development an example of
reciprocal interaction/signalling controlling the morphogenesis of a strucutre
33
what are the stages of the hair cycle
growth (anagen) regression (catagen) rest (telogen). shedding phase (exogen,)
34
what is the length of the hair dependent on
length of anagen phase = proliferation and differentiation of matrix cells at the follicle base
35
descire the transition from telogen to anagen
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
what physically does the catagen stage do
bring the DP closer to the stem cells in the bulge
37
what is required to maintain the HF for life | and how this utilised
the dp kill - stop unwanted hair growth implant - hair transplant
38
what is the role of fgf5 in anagen
ends the anagen phase and promotes catagen | mut - longer anagen - longer hair