Open AccessWNT/β-catenin signaling plays a crucial role in myoblast fusion through regulation of Nephrin expression during development
Author(s) -
Akiko Suzuki,
Ryohei Minamide,
Junichi Iwata
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.168351
Subject(s) - wnt signaling pathway , myogenesis , biology , myocyte , microbiology and biotechnology , catenin , beta catenin , wnt3a , nephrin , signal transduction , genetics , podocyte , proteinuria , kidney
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.