PUBLICATION

Laminins, via heparan sulfate proteoglycans, participate in zebrafish myotome morphogenesis by modulating the pattern of Bmp responsiveness

Authors
Dolez, M., Nicolas, J.F., and Hirsinger, E.
ID
ZDB-PUB-101201-46
Date
2011
Source
Development (Cambridge, England)   138(1): 97-106 (Journal)
Registered Authors
Hirsinger, Estelle
Keywords
Pioneers, Medial fast fibres, engrailed, Phospho-Smad, sleepy, Dorsomorphin, Heparinase, Zebrafish
MeSH Terms
  • Animals
  • Body Patterning/genetics
  • Body Patterning/physiology
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental/genetics
  • Gene Expression Regulation, Developmental/physiology
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/metabolism
  • Heparan Sulfate Proteoglycans/metabolism*
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • In Situ Hybridization
  • Laminin/genetics
  • Laminin/metabolism*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Receptors, Cell Surface/genetics
  • Receptors, Cell Surface/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
21115608 Full text @ Development
Abstract
In zebrafish, Hedgehog-induced Engrailed expression defines a muscle fibre population that includes both slow and fast fibre types and exhibits an organisational role on myotome and surrounding tissues, such as motoneurons and lateral line. This Engrailed-positive population is restricted in the myotome to a central domain. To understand how this population is established, we have analysed the phenotype of the sly/lamc1 mutation in the Laminin γ1 chain that was shown to specifically affect Engrailed expression in pioneers. We find that the sly mutation affects Engrailed expression in the entire central domain and that Hedgehog signalling does not mediate this effect. We show that Bmp-responding cells are excluded from the central domain and that this pattern is modulated by laminins, but not by Hedgehog signalling. Knockdown of Bmp signalling rescues Engrailed expression in the sly mutant and ectopically activates Engrailed expression in slow and fast lineages in wild-type embryos. Last, extracellular matrix-associated heparan sulfate proteoglycans are absent in sly and their enzymatic removal mimics the sly phenotype. Our results therefore show that laminins, via heparan sulfate proteoglycans, are instrumental in patterning Bmp responsiveness and that Bmp signalling restricts Engrailed expression to the central domain. This study underlines the importance of extracellular cues for the precise spatial modulation of cell response to morphogens.
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