Tbx6, Mesp-b and ripply1 regulate the onset of skeletal myogenesis in zebrafish

During embryonic development, the paraxial mesoderm becomes segmented into somites, within which proliferative muscle progenitors and muscle fibers establish the skeletal musculature. Here, we demonstrate that a gene network previously implicated in somite boundary formation, involving the transcriptional regulators Tbx6, Mesp-b and Ripply1, also confers spatial and temporal regulation to skeletal myogenesis in zebrafish. We show that Tbx6 directly regulates mesp-b and ripply1 expression in vivo, and that the interactions within the regulatory network are largely conserved among vertebrates. Mesp-b is necessary and sufficient for the specification of a subpopulation of muscle progenitors, the central proportion of the Pax3+/Pax7+ dermomyotome. Conditional ubiquitous expression indicates that Mesp-b acts by inhibiting myogenic differentiation and by inducing the dermomyotome marker meox1. By contrast, Ripply1 induces a negative-feedback loop by promoting Tbx6 protein degradation. Persistent Tbx6 expression in Ripply1 knockdown embryos correlates with a deficit in dermomyotome and myotome marker gene expression, suggesting that Ripply1 promotes myogenesis by terminating Tbx6-dependent inhibition of myogenic maturation. Together, our data suggest that Mesp-b is an intrinsic upstream regulator of skeletal muscle progenitors and that, in zebrafish, the genes regulating somite boundary formation also regulate the development of the dermomyotome in the anterior somite compartment. © 2015. Published by The Company of Biologists Ltd.

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Development (Cambridge), 142, 6, 1159-1168
animal ; animal cell ; Animals ; anterior posterior axis ; Antibodies ; antibody labeling ; Article ; Base Sequence ; basic helix loop helix transcription factor ; Basic Helix-Loop-Helix Transcription Factors ; cell differentiation ; cell maturation ; chromatin immunoprecipitation ; controlled study ; Danio rerio ; Developmental ; DNA ; DNA sequence ; embryo ; Embryology ; fast muscle fiber ; gene control ; Gene expression ; gene expression regulation ; Gene Knockdown Techniques ; gene regulatory network ; Gene Regulatory Networks ; gene silencing ; Genetically Modified ; Genetics ; heat shock ; high throughput sequencing ; immunohistochemistry ; Immunology ; in situ hybridization ; in vivo study ; marker gene ; meox1 protein ; mesoderm ; mespb protein ; metabolism ; molecular genetics ; Molecular Sequence Data ; Monoclonal ; monoclonal antibody ; morpholino oligonucleotide ; Morpholinos ; Muscle ; muscle development ; myotome ; negative feedback ; nonhuman ; notochord ; nuclear protein ; Nuclear Proteins ; nucleotide sequence ; phenotype ; Physiology ; priority journal ; protein degradation ; protein expression ; protein function ; Reverse Transcriptase Polymerase Chain Reaction ; reverse transcription polymerase chain reaction ; ripply1 protein ; Sequence Analysis ; Skeletal ; skeletal muscle ; slow muscle fiber ; somite ; Somites ; T-Box Domain Proteins ; T box transcription factor ; tbx6 protein ; transcription factor ; transcription factor Mesp b ; transcription factor PAX3 ; transcription factor PAX7 ; transcription factor Ripply1 ; transcription factor TBX6 ; transcription initiation site ; transcription regulation ; transgenic animal ; unclassified drug ; upregulation ; Vertebrata ; zebra fish ; zebrafish ; zebrafish protein ; Zebrafish Proteins

 Record created 2017-05-30, last modified 2018-03-17

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