WNT/β-catenin signaling plays a crucial role in myoblast fusion through regulation of nephrin expression during development

Development. 2018 Nov 27;145(23):dev168351. doi: 10.1242/dev.168351.

Abstract

Skeletal muscle development is controlled by a series of multiple orchestrated regulatory pathways. WNT/β-catenin is one of the most important pathways for myogenesis; however, it remains unclear how this signaling pathway regulates myogenesis in a temporal- and spatial-specific manner. Here, we show that WNT/β-catenin signaling is crucial for myoblast fusion through regulation of the nephrin (Nphs1) gene in the Myog-Cre-expressing myoblast population. Mice deficient for the β-catenin gene in Myog-Cre-expressing myoblasts (Ctnnb1F/F;Myog-Cre mice) displayed myoblast fusion defects, but not migration or cell proliferation defects. The promoter region of Nphs1 contains the conserved β-catenin-binding element, and Nphs1 expression was induced by the activation of WNT/β-catenin signaling. The induction of Nphs1 in cultured myoblasts from Ctnnb1F/F;Myog-Cre mice restored the myoblast fusion defect, indicating that nephrin is functionally relevant in WNT/β-catenin-dependent myoblast fusion. Taken together, our results indicate that WNT/β-catenin signaling is crucial for myoblast fusion through the regulation of the Nphs1 gene.

Keywords: Muscle development; Myoblast fusion; Nephrin; WNT/β-catenin signaling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Fusion
  • Cell Lineage
  • Membrane Proteins / metabolism*
  • Mice
  • Muscle Development*
  • Myoblasts / cytology*
  • Myoblasts / metabolism*
  • Tongue / metabolism
  • Wnt Signaling Pathway*

Substances

  • Membrane Proteins
  • nephrin