ZFIN ID: ZDB-PUB-110517-3
Ret signalling integrates a craniofacial muscle module during development
Knight, R.D., Mebus, K., d'Angelo, A., Yokoya, K., Heanue, T., and Roehl, H.
Date: 2011
Source: Development (Cambridge, England)   138(10): 2015-2024 (Journal)
Registered Authors: Heanue, Tiffany A., Knight, Robert, Mebus, Katharina, Roehl, Henry
Keywords: Tübingen 2000 Screen Consortium, zebrafish, GDNF, head muscle, musculoskeletal
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Biological Evolution
  • DNA Primers/genetics
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Glial Cell Line-Derived Neurotrophic Factor Receptors/deficiency
  • Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics
  • Glial Cell Line-Derived Neurotrophic Factor Receptors/physiology
  • Head
  • Muscle Development/genetics
  • Muscle Development/physiology*
  • Muscle, Skeletal/embryology
  • Mutation
  • Phenotype
  • Proto-Oncogene Proteins c-ret/deficiency
  • Proto-Oncogene Proteins c-ret/genetics
  • Proto-Oncogene Proteins c-ret/physiology*
  • Signal Transduction
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 21490065 Full text @ Development

An appropriate organisation of muscles is crucial for their function, yet it is not known how functionally related muscles are coordinated with each other during development. In this study, we show that the development of a subset of functionally related head muscles in the zebrafish is regulated by Ret tyrosine kinase signalling. Three genes in the Ret pathway (gfra3, artemin2 and ret) are required specifically for the development of muscles attaching to the opercular bone (gill cover), but not other adjacent muscles. In animals lacking Ret or Gfra3 function, myogenic gene expression is reduced in forming opercular muscles, but not in non-opercular muscles derived from the same muscle anlagen. These animals have a normal skeleton with small or missing opercular muscles and tightly closed mouths. Myogenic defects correlate with a highly restricted expression of artn2, gfra3 and ret in mesenchymal cells in and around the forming opercular muscles. ret+ cells become restricted to the forming opercular muscles and a loss of Ret signalling results in reductions of only these, but not adjacent, muscles, revealing a specific role of Ret in a subset of head muscles. We propose that Ret signalling regulates myogenesis in head muscles in a modular manner and that this is achieved by restricting Ret function to a subset of muscle precursors.