期刊
DEVELOPMENT
卷 142, 期 6, 页码 1159-1168出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.113431
关键词
Dermomyotome; Myotome; Segmentation; Maturation; Zebrafish; Heat shock; Protein degradation; Determination front; Wavefront; Gene regulatory network
资金
- National Institutes of Health (NIH) [R01 HD37509]
- Max Planck Society
- European Research Council (ERC) under the European Communities 7th Framework Programme [FP7]/ERC [207634]
- Wellcome Trust [WT098025MA]
- Medical Research Council [MC_UP_1202/3]
- EMBO long-term fellowship [ALTF 1572-2011]
- Lister Institute for Preventive Medicine Research Prize
- A*STAR Graduate Academy scholarship
- British Heart Foundation [PG/13/19/30059] Funding Source: researchfish
- Cancer Research UK
- The Francis Crick Institute [10124] Funding Source: researchfish
- Medical Research Council [MC_UP_1202/3] Funding Source: researchfish
- MRC [MC_UP_1202/3] Funding Source: UKRI
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.
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