ß-catenin is essential for differentiation of primary myoblasts via cooperation with MyoD and a-catenin.

Shuang Cui, Liang Li, Ruth T. Yu, Michael Downes, Ronald M. Evans, Julie-Ann Hulin, Helen Makarenkova, Robyn Meech

Research output: Contribution to journalArticle

2 Citations (Scopus)
2 Downloads (Pure)

Abstract

Canonical Wnts promote myoblast differentiation; however, the role of β-catenin in adult myogenesis has been contentious, and its mechanism(s) unclear. Using CRISPR-generated β-catenin-null primary adult mouse myoblasts, we found that β-catenin was essential for morphological differentiation and timely deployment of the myogenic gene program. Alignment, elongation and fusion were grossly impaired in null cells, and myogenic gene expression was not coordinated with cytoskeletal and membrane remodeling events. Rescue studies and genome-wide analyses extended previous findings that a β-catenin-TCF/LEF interaction is not required for differentiation, and that β-catenin enhances MyoD binding to myogenic loci. We mapped cellular pathways controlled by β-catenin and defined novel targets in myoblasts, including the fusogenic genes myomaker and myomixer. We also showed that interaction of β-catenin with α-catenin was important for efficient differentiation. Overall the study suggests dual roles for β-catenin: a TCF/LEF-independent nuclear function that coordinates an extensive network of myogenic genes in cooperation with MyoD; and an α-catenin-dependent membrane function that helps control cell-cell interactions. β-Catenin-TCF/LEF complexes may function primarily in feedback regulation to control levels of β-catenin and thus prevent precocious/excessive myoblast fusion.

Original languageEnglish
Article numberdev167080
Number of pages11
JournalDevelopment
Volume146
Issue number6
DOIs
Publication statusPublished - 19 Mar 2019

Bibliographical note

Made available in accordance with publishers user license 1.1. Electronic version subject to 12 month embargo.

Keywords

  • Homeobox genes
  • Muscle stem cells
  • Moygenesis
  • Skeletal muscle
  • Transcription factors
  • Epigenetics

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