3.2

subdivisions of somites

recall that when cells are born out of the tailbud region, they alr know their

R/C axis from differential Mesp2 expression and A/P from differential Hox gene expression

the first couple somites contribute to the base of the skull, so we are ignoring them for this class

somites form

R—>C

EMT is used to make

sclerotome

medial dermamyotome becomes the

• primaxial/epaxial skeletal muscles (muscles at the base of the skull)

• intercostal muscles

• intevertebral muscles of the back

central dermamyotome becomes

• dermis of the back

• brown fat

• muscle stem cells (satellite cells)

lateral dermamyotome becomes

• abaxial/hypaxial skeletal muscles (ventral skeletal muscle of the body wall)

• diaphragm

• limb musculature

• tongue

sclerotome becomes

• cartilage

• bone

• tendons of axial skeleton

somitocoel cells become

• outer part of intervertebral disks

• satellite cells

3 parts of dermamyotome

• medial

• central

• lateral

brown fat

regulates/maintains high temp by decoupling ATP in oxidative phsophorylation

satellite cells

help make more muscle

central dermamyotome does not contribute to any

skeletal muscle (unlike medial and lateral dermamyotome)

after they form, somites are patterned along their

D/V and medial/lateral (M/L) axes

• somites are not born with these axes

Exps that showed us that DV and ML axes are acquired after formation of somites

• somite explantation and rotation

• if flipped 180º, somites form per normal if from a younger somite (0) but NOT if in an older somite (S3/4), which already specified its DV axes

• if do same thing in young cell, no change, but flips ML axis if S5/6

• so something happens between these somite stages

• ML is acquired after DV axis

• someite explantation Exps: S1-3 express Pax3 but older somites 4-5 express Pax1 in sclerotome but Pax3 in dermamyotome (so dorsal is normal and ventral is induced state)

medial dermamyotime expresses skeletal muscles earlier than

lateral

• so ML is a function of time

ML is a consequence of

BMP gradient

• BMP coming from lateral and inhibitors more medially

D/V patterning

ventral has high Shh from notochord and ventral part of the neural tube

• Wnt is high dorsally

high concentrations of ______ from the notochord induce the V side

Shh

• grafted notochord to dorsal location, and ventralized scelrotome forms dorsally

EMT helps form

sclerotome

dermamyotome is more

dorsal

myotome formation (skeletal muscle cells)

• earliest marker of commitment to this lineage is MyoD or Myf5 (TFs that lead to skeletal muscles)

• myoblasts do EMT to underneath the dermamyotome to form dermamyotome

• stop dividing and fuse to form multinucleated skeletal muscle fibers

in mice, Myf5 turns on first and activates MyoD

in chx, the reverse occurs: MyoD turns on first and activates Myf5

primaxial/epaxial muscles

• epaxial comes from DML (dorsal medial lip) of the dermamyotome and forms axial skeletal muscles

  • muscles at base of skull, intercostal muscles, most intevertebral muscles of the back

  • stuff from DML commits sooner to its given lineage than things from the VLL

abaxial/hypaxial skeletal muscles

hypaxial form from the VLL (ventro-lateral lip of the dermamyotome)

• migrate away and become skeletal muscles of the ventral body wall (abs), diaphragm, limb, tongue

• so determined after they get the the correct location

2 types of somite-derived skeletal muscle

• primaxial/epaxial

• abaxial/hypaxial

DML gives rise to

epaxial/primaxial myotome THEN epaxial/primaxial skeletal muscle

VLL becomes

abaxial/hypaxial myotome THEN abaxial/hypaxial skeletal muscle

primaxial/epaxial

comes from DML

primaxial vs abaxial

primaxial: from medial part of dermamyotome

abaxial: from lateral part of dermamyotome

epaxial vs hypaxial

epaxial: innervated by dorsal ramus

hypaxial: innervated by ventral ramus$

• based on how these muscles are later innervated

although epaxial vs hypaxial and primaxial vs abaxial have diff meanings,

we just say that primaxial is epaxial and abaxial is hypaxial

• they are not quite synonyms, but are just saying that they are

initiation of epaxial skeletal muscle

• little bit of Shh from notochord and ventral part of the neural tube, which primes these cells to later respond to Wnt from dorsal neural tube and ectoderm

• Myf5 or MyoD activated first and activates the other

• later decr in BMP prepares myoblasts for EMT (migrate down)

• DML also produces Noggin (activated by Wnt), which —| BMP (to get BMP lower and initiate the EMT)

• to actually move down, must be coordinated with movement of neural crest cells as well (reciprocal interactions between the two)

lateral part of dermamyotome is too far from neural tube and notochord to receive

much Shh

myotome precursors cells must undergo EMT to form myotome at same time as

neural crest cells that left dorsal part of neural tube get into the same area

• coordinated via a Notch-Delta high-five interaction

• Delta is on neural crest cells

• DML (dorsal medial lip) cells express Notch

• they touch each other and undergo EMT and continue along their journey

• so their contact is what initiates their EMT to continue migrating

• so cross-talk between somite-derived and neural tube-derived cells

abaxial/hypaxial muscles differentiation does not occur until

these cells are out in the periphery

• delayed by BMP4 from LPM so that the cells migrate to their location before differentiating

• lots of BMP4 laterally

• once they get laterally, they get Wnt and Shh that initiate myogenesis in the limb bud area

central dermamyotome becomes

dermis

• responding to later signals of ectoderm and NT

cartilage vs tendon differentiation

sclerotome becomes the cartilage and tendon

• early FGF goes sclerotome from myotome

• myotome laterally secretes Fgf8, and shifts dorsal-most sclerotome from cartilage path to a tendon path

• other sclerotome cells that didn’t get Fgf8 go cartilage path

vertebrae are mostly derived from sclerotome, and sme from

notochord itself

• inner part of each intervetebral disk (nucleus pulposus) is from notochord

dermamyotome makes

skeletal muscle

how to offset muscle vs bone to form vertebrate organization the way it is in adults

• must offset sclerotome and myotome derivatives so that bone and muscle alternate (resegmentation)

• sclerotome moves while dermamyotome stays put

• sclerotome moves differently if from A or P side of embryo

vertebrate formation/resegmentation

• sclerotome cells precursor split A/P sides themselves

• each vertebrate comes from two diff somites

• rostral half of one somite and the caudal half of another fuse to form a single vertebrate (resegmentation)

segmentation

makes somites

resegmentation

splitting sclerotome into R/C or A/P halves to form the vertebrae

vertebrate derivatives

sclerotome—> vertebral body

notochord—> central part of intervertebral cushions (nucleus pulposus)

somitocoel OR sclerotome—> anulus fiberosus (outer part of intervertebral disks)