The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling

Nat Genet. 2004 Jan;36(1):88-93. doi: 10.1038/ng1280. Epub 2003 Dec 21.


Vertebrate skeletal muscles comprise distinct fiber types that differ in their morphology, contractile function, mitochondrial content and metabolic properties. Recent studies identified the transcriptional coactivator PGC-1alpha as a key mediator of the physiological stimuli that modulate fiber-type plasticity in postembryonic development. Although myoblasts become fated to differentiate into distinct kinds of fibers early in development, the identities of regulatory proteins that determine embryonic fiber-type specification are still obscure. Here we show that the gene u-boot (ubo), a mutation in which disrupts the induction of embryonic slow-twitch fibers, encodes the zebrafish homolog of Blimp-1, a SET domain-containing transcription factor that promotes the terminal differentiation of B lymphocytes in mammals. Expression of ubo is induced by Hedgehog (Hh) signaling in prospective slow muscle precursors, and its activity alone is sufficient to direct slow-twitch fiber-specific development by naive myoblasts. Our data provide the first molecular insight into the mechanism by which a specific group of muscle precursors is driven along a distinct pathway of fiber-type differentiation in response to positional cues in the vertebrate embryo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • DNA-Binding Proteins / physiology*
  • Hedgehog Proteins / physiology*
  • Molecular Sequence Data
  • Muscle Fibers, Slow-Twitch / physiology*
  • Nuclear Proteins
  • Positive Regulatory Domain I-Binding Factor 1
  • Repressor Proteins / physiology*
  • Signal Transduction
  • Transcription Factors / physiology*
  • Zebrafish / embryology*
  • Zebrafish Proteins / physiology*


  • DNA-Binding Proteins
  • Hedgehog Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Transcription Factors
  • Zebrafish Proteins
  • peroxisome proliferator activated receptor gamma coactivator-1alpha, zebrafish
  • ubo8 protein, Papio hamadryas
  • Positive Regulatory Domain I-Binding Factor 1
  • prdm1a protein, zebrafish