PUBLICATION

Fine-tuning of Hh signaling by the RNA-binding protein Quaking to control muscle development

Authors
Lobbardi, R., Lambert, G., Zhao, J., Geisler, R., Kim, H.R., and Rosa, F.M.
ID
ZDB-PUB-110429-22
Date
2011
Source
Development (Cambridge, England)   138(9): 1783-1794 (Journal)
Registered Authors
Geisler, Robert, Kim, Rosemary, Lambert, Guillaume, Rosa, Frederic, Zhao, Jue
Keywords
quaking, hedgehog, Gli2a, muscle specification, RNA-binding protein, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/genetics
  • Body Patterning/physiology
  • Chromosome Mapping
  • Embryo, Nonmammalian
  • Genes, Recessive
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/metabolism
  • Hedgehog Proteins/physiology*
  • Morphogenesis/genetics
  • Morphogenesis/physiology
  • Muscle Development/genetics*
  • Muscle Development/physiology
  • Muscle Fibers, Fast-Twitch/metabolism
  • Muscle Fibers, Fast-Twitch/physiology
  • Muscle Fibers, Slow-Twitch/metabolism
  • Muscle Fibers, Slow-Twitch/physiology
  • Mutation/physiology
  • RNA-Binding Proteins/genetics
  • RNA-Binding Proteins/physiology*
  • Signal Transduction/genetics
  • Signal Transduction/physiology
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed
21447554 Full text @ Development
Abstract
The development of the different muscles within the somite is a complex process that involves the Hedgehog (Hh) signaling pathway. To specify the proper number of muscle cells and organize them spatially and temporally, the Hh signaling pathway needs to be precisely regulated at different levels, but only a few factors external to the pathway have been described. Here, we report for the first time the role of the STAR family RNA-binding protein Quaking A (QkA) in somite muscle development. We show in zebrafish that the loss of QkA function affects fast muscle fiber maturation as well as Hh-induced muscle derivative specification and/or morphogenesis. Mosaic analysis reveals that fast fiber maturation depends on the activity of QkA in the environment of fast fiber progenitors. We further show that Hh signaling requires QkA activity for muscle development. By an in silico approach, we screened the 3'UTRs of known Hh signaling component mRNAs for the Quaking response element and found the transcription factor Gli2a, a known regulator of muscle fate development. Using destabilized GFP as a reporter, we show that the gli2a mRNA 3'UTR is a functional QkA target. Consistent with this notion, the loss of QkA function rescued slow muscle fibers in yot mutant embryos, which express a dominant-negative Gli2a isoform. Thus, our results reveal a new mechanism to ensure muscle cell fate diversity by fine-tuning of the Hh signaling pathway via RNA-binding proteins.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping