PUBLICATION

The zebrafish slow-muscle-omitted gene product is required for Hedgehog signal transduction and the development of slow muscle identity

Authors
Barresi, M.J., Stickney, H.L., and Devoto, S.H.
ID
ZDB-PUB-000505-14
Date
2000
Source
Development (Cambridge, England)   127(10): 2189-2199 (Journal)
Registered Authors
Barresi, Michael J. F., Devoto, Stephen Henri, Stickney, Heather
Keywords
slow muscle; muscle fiber type; zebrafish; muscle pioneer; axial muscle; Hedgehog signaling; slow-muscle-omitted; smoothened; patched; protein kinase A; forskolin
MeSH Terms
  • Animals
  • Colforsin
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Gene Expression
  • Genes
  • Hedgehog Proteins
  • Muscle Fibers, Slow-Twitch/physiology*
  • Muscle Proteins/genetics
  • Muscle Proteins/metabolism
  • Muscle, Skeletal/embryology*
  • Mutagenesis
  • Phenotype
  • Proteins/genetics
  • Proteins/metabolism*
  • Rats
  • Receptors, Cell Surface/genetics
  • Receptors, G-Protein-Coupled*
  • Signal Transduction*/genetics
  • Trans-Activators*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins*
PubMed
10769242 Full text @ Development
Abstract
Hedgehog proteins mediate many of the inductive interactions that determine cell fate during embryonic development. Hedgehog signaling has been shown to regulate slow muscle fiber type development. We report here that mutations in the zebrafish slow-muscle-omitted (smu) gene disrupt many developmental processes involving Hedgehog signaling. smu(-)(/)(-) embryos have a 99% reduction in the number of slow muscle fibers and a complete loss of Engrailed-expressing muscle pioneers. In addition, mutant embryos have partial cyclopia, and defects in jaw cartilage, circulation and fin growth. The smu(-)(/)(-) phenotype is phenocopied by treatment of wild-type embryos with forskolin, which inhibits the response of cells to Hedgehog signaling by indirect activation of cAMP-dependent protein kinase (PKA). Overexpression of Sonic hedgehog (Shh) or dominant negative PKA (dnPKA) in wild-type embryos causes all somitic cells to develop into slow muscle fibers. Overexpression of Shh does not rescue slow muscle fiber development in smu(-)(/)(-) embryos, whereas overexpression of dnPKA does. Cell transplantation experiments confirm that smu function is required cell-autonomously within the muscle precursors: wild-type muscle cells rescue slow muscle fiber development in smu(-)(/)(-) embryos, whereas mutant muscle cells cannot develop into slow muscle fibers in wild-type embryos. Slow muscle fiber development in smu mutant embryos is also rescued by expression of rat Smoothened. Therefore, Hedgehog signaling through Slow-muscle-omitted is necessary for slow muscle fiber type development. We propose that smu encodes a vital component in the Hedgehog response pathway.
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