title: The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling.
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.
authors.affiliation: MRC Intercellular Signaling Group, Center for Developmental Genetics, School of Medicine and Biomedical Sciences, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baxendale
authors.forename: Claire
authors.initials: C
authors.lastname: Davison
authors.forename: Claire
authors.initials: C
authors.lastname: Muxworthy
authors.forename: Christian
authors.initials: C
authors.lastname: Wolff
authors.forename: Philip W
authors.initials: PW
authors.lastname: Ingham
authors.forename: Sudipto
authors.initials: S
authors.lastname: Roy
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology*; D053823:Hedgehog Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology*; D009687:Nuclear Proteins; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D009687:Nuclear Proteins; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C572938:ppargc1a protein, zebrafish; C104440:ubo8 protein, Papio hamadryas; C513257:prdm1a protein, zebrafish