BIOL 1F25 Lecture Notes - Myod, Tx Network, Myostatin

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Outline of Lecture 11
Muscle Development
I. There are four muscle types
- They are: skeletal, cardiac, smooth, myoepithelial
- Classic stuff: review structural and functional differences of the muscle types
- Skeletal muscles can specialize; in vertebrates, there are slow and fast twitch
- Specialization is due to isoforms of muscle structural proteins
- Function of myoepithelial is to expel secretions from various glands and dilate
iris of eye
II. Embryology of muscle
- See Lecture 08 on mesoderm formation; details on tissue types that arise are also
on p.3-4 here
- Paraxial, intermediate, and lateral plate mesoderm
- Somite formation
- Arises from paraxial meso., divides into sclero-, myo-, dermatome
(medial to lateral)
- Somitomeres become somites upon mesenchymal to epithelial transition
- First (anterior) 7 remain somitomeres, rest become somites
- Myotome gives rise to myogenic cells of the epimere (dorsal, spine extensor
muscles) and hypomere (ventral by migration, body wall muscles)
- Where muscles arise from
- Head skeletal: somitomeres and somites of paraxial meso. that migrate to
branchial arch
- Limb skeletal: entirely from somites; muscle fate is determine by contact with
connective tissue
- Smooth: mesenchymal cells from splanchic mesoderm
- Cardiac: splanchnic mesoderm around endothelial heart tube
- Myoepithelial: ectoderm (not mesoderm!)
III. Muscle differentiation
- Myoblasts (which can be distinguished from fibroblasts) divide then fuse to
form what develops into a skeletal muscle fiber
- MyoD family directs cells to develop into muscles
- Screen cDNA library from young myoblasts in multipotential 10T1/2 cells to
find genes that cause cells to develop into muscles
- MyoD identified this way, a txn factor with conserved bHLH
- MyoD family has 4 members: MyoD, myf5, myogenin, MRF4
- Active MyoD is a dimer (esp. with E12); can be inhibited as inactive
- MyoD and myf5 are expressed early, determine fate, and regulate myogenin;
myogenin and MRF4 are needed later for differentiation and maturation
- The MEF-2 family of txn factors control muscle-specific gene expr
- MEF-2 may be regulated by myogenin
- Determinants from tissue around myotome also direct development
- Shh from notochord/floor plate may block myotome development
- Wnt from dorsal neural tube may induce muscle fate
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