L20-21: Somatogenesis Flashcards
Which mesoderm do somites come from?
paraxial mesoderm
What direction do the the somite formation happen in?
anterior to posterior
What type of cells are somites before they become somites? and what process do they go through?
mesenchymal. MET
What is naggin?
BMP inhibitor. This is required specifically for somite development
Which transcription factor detects inhibition of BMP to promote somite development?
Pax3
Only the surface mesoderms turn into epithelial tissues. True or False?
True. It forms into a ball shape that are identical in size
Do somites form in a timely manner?
Yes. they form in a species specific time frame (90 min in chicken)
What are the five steps in somite formation
- periodicity
- cell boundaries
- epitheliailization
- specification
- differentiation
How do you prove that somite patterns are inherent in mesenchymal cells?
transplating border mesenchymal cells in non border regions cause new border formation.
Transplanting non-border cells in the same way doesnt produce any changes
Describe notch signalling
- Notch and delta binds
- Notch comformational change
- notch cytoplasmic domain cleaved by presenilin
- you
Describe notch signalling
- Notch and delta binds
- Notch comformational change
- notch cytoplasmic domain cleaved by presenilin
- cleaved notch part becomes a transcriptional factor
Is notch signalling essential for somite formation?
YES. or the poor mice get fked
How can we test for what happens if notch signalling didn’t happen through experimentation.
inactivate presenilin
What are some downstream effectors of notch?
Hes 1, Hes 7, Hairy 1, Lunatic frindge
How often are new somites created in chicks?
90 min
Which downstream effector of notch is seen oscillating in during somite formation every 90 min?
Hairy1, wnt
What are three other pathways that undergo oscilation during development of somites?
Dkk1 - extracellular signalling of wnt
Dact - intracellular signal transduction of wnt
Axin2 - inhibition of wnt
Axin2 and notch signalling. Which is dependent on the other?
Notch signalling is dependent on Axin2 (wnt) signalling as it precedes notch signalling in cycles
Describe the opposing gradient that occurs during each cycle.
Raldh2 -> RA
Fdf8 -> FGF
Describe the opposing gradient that occurs during each cycle.
Raldh2 -> RA > differentiation
Fdf8 -> FGF > suppress differentiation
anterior side with RA gradient
posterior side with FGF gradient
midline is the boundary
What is the middle of RA and FGF gradient called?
Determination front
Describe eph pathway involvement in somatogenesis
ephrin B2 in anterior cell bottom
eph A4 in posterior cell top
notch triggers this pathway
Are all muscles derived from somites?
No. Everything except head muscles
What are the back muscles formed from? What are the signals required for this development?
Primaxial myotome.
shh from notochord, wnt from neural tube
What are the limbs and body wall muscles formed from? What are the signals required for this development?
abaxial myotome
wnt from epidermis, other factors from lateral mesoderm
What does shh contribute in?
primaxial myotome, sclerotome
What are internal genes that are turned on in paraxial myotome, abaxial myotome and sclerotome?
myf5
myoD, pax3
Pax1
describe wnt and hedgehog signalling
without wnt
- activate GSK3β complex > β catenin degraded > no transcription
with wnt
- no active GSK3β > β catenin removes groucho > transcription
One day 2-3 which part goes through EMT? what does it form into?
Ventral medial cells (sclerotome) goes through EMT.
Turns into cartilage
On which day of the embryo do we get myotome and sclerotome differentiation?
2-3 days
Does myocyte elongation happen from only one side?
No from all 4 sides. can be seen with GFP for 48 hours.
Does central myotome invade into primary myotome? are they differentiated before after? What do they express?
Yes. Can be seen with GFP. They are no differntiated. and they express Pax7
Which parthway in primary myotome promotes EMT?
FGF > snail
On which day is abaxial somatic bud and primaxial somatic lip formed?
late Day 4
Which two pathways trigger central dermamyotome to EMT? and which way do they migrate aftewards?
wnt6, Neurotrophin-3. (from neural tube)
Up towards beneath epidermis
Trigger for central dermamyotome comes through wnt6 and NT3 comes from where?
dorsal neural tube
4 types of muscle cells
- Striated (in myoneural junction)
- Cadiac muscle fibres
- Myoepithelial cells (milk ducts, salivary glands)
- Smooth muscle cells on collagen
How does limb and interlimb differ in abaxial EMT?
in interlimb, abaxial delamination produces limbs.
in interlimb, lateral dermamyotome migrates to underlying myotome.
Explain pathways in limb budding
From limb (FGF > HGF > c-met) From abaxial myotome (Pax3 > MyoD)
At limb target sites, does differentiation or proliferation happen first?
proliferation
What are myotubes formed from?
multiple myoblasts joining together
Does the number of myoblasts increase from birth to adulthood?
No.
They grow by fusing with single nucleated myoblasts (1st week)
Then grow my stretching with actin and myosin filaments
cell fusion is referred to as?
syncytium
What are the five steps in striated muscle cell formation. Along with signals needed in each step
- myotome cell (determination).
bHLH > lineage specification with myoD, Myf5 > Myogenin and MRF4 - dividing myotoblasts
FGF - cell alignment (no more FGF)
Fibronectin, integrins, cadherins
myogenins > transcription of muscle specific genes - myotube formation > maturation
myoferlin & dysferlin
muscle MMP
IL-4 for myoblast fusion with myotube
During myotube maturation, what is required? Which exact molecule is it needed by?
myoferlin with Ca2+
What is the purpose of myostatin? What happens without it?
inhibits myogenesis (proliferation to differentiation) Without it, hyperplasia (more fibre), hypertropy (big muscle)
myostatin is in which family of growth factor?
TGFβ
Are myofibres surrounded by basal lamina? What is located in between these?
Yes. satellite cells
What is another name of putative muscle stem cell?
satellite cell
What are the functions of satellite cells?
self renewal, injury recovery, proliferation in response to stress/exercise
Satellite cells are derived from which part of the somite?
central dermamyotome
Satellite cells express what?
Pax3 and Pax7
Satellite cells do not express what and why?
bHLH, myoD and myf5. Else it would differentiate all the time
What is expressed in daughter satellite cell that divide?
Myf5 and myoD
Which two structures are located on basal lamina to attach to actin filament?
integrin and dystroglycan
What does RA promote or suppress? what is its gene?
promote cell differentiation. Raldh2
What does FGF promote or suppress? What is its gene?
Suppresses cell differentiation. fgf8
