Nature Genetics36, 88 - 93 (2004)
Published online: 21 December 2003; | doi:10.1038/ng1280
The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling
Sarah Baxendale1, Claire Davison1, Claire Muxworthy1, Christian Wolff1, Philip W Ingham1
& Sudipto Roy1, 2
1
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.
2
Institute of Molecular and Cell Biology, 30 Medical Drive, 117609 Singapore.
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-1 as a key mediator of the physiological stimuli that modulate fiber-type plasticity in postembryonic development1. 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 fibers2, encodes the zebrafish homolog of Blimp-1, a SET domain−containing transcription factor that promotes the terminal differentiation of B lymphocytes in mammals3. 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.
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