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.

Abstract

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*

Substances

  • 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