miR-133-mediated regulation of the Hedgehog pathway orchestrates embryo myogenesis

Mok, Gi Fay ORCID: https://orcid.org/0000-0002-5202-9062, Lozano-Velasco, Estefania, Maniou, Eirini, Viaut, Camille, Moxon, Simon ORCID: https://orcid.org/0000-0003-4644-1816, Wheeler, Grant ORCID: https://orcid.org/0000-0002-4335-8577 and Münsterberg, Andrea ORCID: https://orcid.org/0000-0002-4577-4240 (2018) miR-133-mediated regulation of the Hedgehog pathway orchestrates embryo myogenesis. Development, 145 (12). ISSN 0950-1991

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Skeletal myogenesis serves as a paradigm to investigate the molecular mechanisms underlying exquisitely regulated cell fate decisions in developing embryos. The evolutionary conserved miR-133 family of microRNAs is expressed in the myogenic lineage, but how it acts remains incompletely understood. Here we performed genome-wide differential transcriptomics of miR-133 knock-down (KD) embryonic somites, the source of vertebrate skeletal muscle. This revealed extensive downregulation of Sonic hedgehog (Shh) pathway components: patched receptors, Hedgehog interacting protein, and the transcriptional activator, Gli1. By contrast Gli3, a transcriptional repressor, was de-repressed and confirmed as a direct miR-133 target. Phenotypically, miR-133 KD impaired myotome formation and growth by disrupting proliferation, extracellular matrix deposition and epithelialization. Together this suggests that miR-133 mediated Gli3 silencing is critical for embryonic myogenesis. Consistent with this idea we found that activation of Shh signalling by either purmorphamine, or KD of Gli3 by antisense morpholino (MO) rescued the miR-133 KD phenotype. We identify a novel Shh/MRF/miR-133/Gli3 axis that connects epithelial morphogenesis with myogenic fate specification.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Cells and Tissues
Faculty of Science > Research Groups > Wheeler Group
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Depositing User: Pure Connector
Date Deposited: 01 Jun 2018 10:30
Last Modified: 20 Apr 2023 02:35
URI: https://ueaeprints.uea.ac.uk/id/eprint/67261
DOI: 10.1242/dev.159657


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