ZFIN ID: ZDB-PUB-081029-9
Specification of vertebrate slow-twitch muscle fiber fate by the transcriptional regulator Blimp1
Liew, H.P., Choksi, S.P., Wong, K.N., and Roy, S.
Date: 2008
Source: Developmental Biology   324(2): 226-235 (Journal)
Registered Authors: Liew, Hoe Peng, Roy, Sudipto
Keywords: Myotome, Myoblast, Zebrafish, Slow-twitch muscle, Fast-twitch muscle, Hedgehog, Blimp1, Slow Myosin heavy chain, Prox1, Fast Myosin light chain
MeSH Terms:
  • Animals
  • Animals, Genetically Modified/embryology
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/metabolism
  • Binding Sites
  • Cardiac Myosins/genetics
  • Cardiac Myosins/metabolism
  • Cell Differentiation
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental
  • Mice
  • Muscle Development/genetics*
  • Muscle Fibers, Slow-Twitch/metabolism*
  • Myoblasts, Skeletal/metabolism
  • Myosin Light Chains/genetics
  • Myosin Light Chains/metabolism
  • Nuclear Proteins/genetics
  • Nuclear Proteins/metabolism*
  • Promoter Regions, Genetic
  • Transcription, Genetic
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 18948093 Full text @ Dev. Biol.
Skeletal muscles of vertebrates are typically composed of slow- and fast-twitch fibers that differ in their morphology, gene expression profiles, contraction speeds, metabolic properties and patterns of innervation. During myogenesis, how muscle precursors are induced to mature into distinct slow or fast-twitch fiber-types is inadequately understood. We have previously shown that within the somites of the zebrafish embryo, the activity of the zinc finger and SET domain containing transcriptional regulator Blimp1 is essential for the specification of slow muscle fibers. Here, we have investigated the mechanism by which Blimp1 programs myoblasts to adopt the slow-twitch fiber fate. In slow myoblasts, expression of the Blimp1 protein is transient, and precedes the expression of slow muscle-specific differentiation genes. We demonstrate that the competence of somitic myoblasts to commit to the slow lineage in response to Blimp1 changes as a function of developmental time. Furthermore, we provide evidence that mammalian Blimp1 can recapitulate the slow myogenic program in zebrafish, suggesting that zebrafish Blimp1 can recognize the same consensus DNA sequence that is bound by the mammalian protein. Finally, we show that zebrafish Blimp1 can repress the expression of fast-muscle-specific myosin light chain, mylz2, through direct binding near the promoter of this gene, indicating that an important function of the transcriptional activity of Blimp1 in slow muscle development is the suppression of fast-muscle-specific gene expression. Taken together, these findings provide new insights into the molecular basis of vertebrate muscle fiber-type specification, and underscore Blimp1 as the central determinant of this process.