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Generation of Myospheres From hESCs by Epigenetic Reprogramming
Published on: June 21, 2014
Sonic hedgehog controls epaxial muscle determination through Myf5 activation
A G Borycki1, B Brunk, S Tajbakhsh
1Department of Cell Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058, USA.
Summary
Sonic hedgehog (Shh) is crucial for activating Myf5 and MyoD genes, essential for deep back muscle development in mouse embryos. Shh also supports survival of specific somite and neural tube cells.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Sonic hedgehog (Shh) is a signaling molecule involved in embryonic development.
- Its role in somite myogenesis, particularly in activating myogenic determination genes, requires further elucidation.
Purpose of the Study:
- To investigate the specific functions of Shh during somite myogenesis in mouse embryos.
- To determine Shh's role in the activation and regulation of myogenic genes Myf5 and MyoD.
Main Methods:
- Analysis of Myf5 and MyoD gene expression in Shh null embryos.
- Examination of presomitic mesoderm explants from wild-type and Myf5 null embryos.
- Assessment of cell survival and proliferation in response to Shh signaling.
Main Results:
- Shh is essential for the early activation of Myf5 and MyoD in epaxial somite cells, crucial for deep back muscle progenitors.
- Shh is not required for myogenesis in hypaxial, limb, or head muscles.
- Shh establishes and maintains medio-lateral gene expression boundaries within somites.
- Myf5, not MyoD, is the direct target of Shh signaling in epaxial myogenesis.
- Shh is vital for the survival of sclerotomal cells and adjacent neural tube cells, but not for epaxial myogenic progenitor survival or proliferation.
Conclusions:
- Shh plays a critical inductive role in activating epaxial myogenesis via Myf5.
- Shh also exerts trophic functions, essential for the survival of sclerotome and neural tube cells.
- These findings highlight the multifaceted roles of Shh in somite patterning and differentiation.
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