Lecture 6 skin appendages Flashcards
what layers does the skin consist of
name some cell type
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
what are appendages
protruding structures that augment the skins primary fucntions
what are placdes
characterisitc condensations of both mesenchymal and ectodermal derived cells which in/e vaginate
beginning of all appendages
what are the cell types and nature of the epidermis
outer layer- enucleated keratinocytes which are continuously shed
once every 4 weeks replaced
where are stem cells of the skin that replace the epidermis
basal layer of the epidermis and bulge of hair follicles
how do the tem cells in teh epidermis replace the keratinocytes
asym div them amplification and migrate away from the basal layer terminally differentiate
rate of production compensates rate of loss
what T is required for the development of the epidermis
p63
req for the stratification in the embryonic ectoderm and for epidermal stem cell specification
what does knockdown experiments of p63 with siRNA show
in control - see the thickening of the differentiated cells
in the treatment ni proliferation and differentation
what axis has been found to regulate the stem cell to TA cel transition
Rac1-Miz axis
describe the Rac1-Miz axis
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.
what roles does Wnt have in homeostaiss of stme cell fate
stem cell specification,
stem cell activation
terminal differentiation.
what is the notch activity expression in the cells of the skin
highest in the spinous cells (switch on Hes1)
lowest in teh basal cells and granular cells
(gradient highest in mid decr either side)
what is the role of notch elucidating from its expr pattern
regulate cell fate decision from Ta cell to spinous cell fate
mesenchymal and epithelial cells make up most organs
what two distinct role do both cell types normally have
speciailised cells normally epithelial
mesenchymal cells = supporting role and send inductive signals to the epithelium
wat are the steps of hari follicles development
placode formation
follicle maturation
when does placode formation occur
In mouse being E14.5
both layers thicken and the epi invag the mesenchyme
a morpho change
what happens when epithelial and mesenchymal cells in culture seprated
survive but no follicle formation
describe the hari follicle structure
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
what cell type is the hair follicle consist of
most epithelial
but mesenchyme contribute to DP
what does tes reversing the epithial layer on mesenchyme result in and what does this show
epithelial placodes disapera
the mesenchyme placodes remaai- mesenchyme controls the placode postion
what is the signal from the mesenchyme thought to be for placode postioning and what some propeties of it
potentially a Wnt
B catenin ko or DKK1 tgics do not develop HF
overexpr b cat - ectopic HF
continuously produced
what is thought to be the singal from the epithelia to the mesenchyme
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
summarise the signals for the formation of hair follicle
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
what sort of positional information contols the pattern formation of hair spacing
(note - all cells capable of becoming Hf)
relative (removing pieces of ski does not affect = spaceing generated locally)
(note limb is absolute as if remove big effect on final ptype )
what mechanism controls spcing of hari follicles
lateral inhibiton
what evidence is there for BMP as the inh signal of hair spacing
ectopic expr - no hair
ko - lots of hair
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
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
give examples of regional signals for appendages
LEF1 - hair
Sweat glands characterised by BMP (ko - sweat glands dev)
what gives the species specific information
the epithelium
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
what is HF development an example of
reciprocal interaction/signalling controlling the morphogenesis of a strucutre
what are the stages of the hair cycle
growth (anagen)
regression (catagen)
rest (telogen).
shedding phase (exogen,)
what is the length of the hair dependent on
length of anagen phase = proliferation and differentiation of matrix cells at the follicle base
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.
what physically does the catagen stage do
bring the DP closer to the stem cells in the bulge
what is required to maintain the HF for life
and how this utilised
the dp
kill - stop unwanted hair growth
implant - hair transplant
what is the role of fgf5 in anagen
ends the anagen phase and promotes catagen
mut - longer anagen - longer hair
