| RRC ID |
54419
|
| 著者 |
Cui S, Li L, Yu RT, Downes M, Evans RM, Hulin JA, Makarenkova HP, Meech R.
|
| タイトル |
β-Catenin is essential for differentiation of primary myoblasts via cooperation with MyoD and α-catenin.
|
| ジャーナル |
Development
|
| 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.
|
| 巻・号 |
146(6)
|
| 公開日 |
2019-3-19
|
| DOI |
10.1242/dev.167080
|
| PII |
dev.167080
|
| PMID |
30683662
|
| PMC |
PMC6451316
|
| MeSH |
Animals
Cell Differentiation
Cell Membrane / metabolism
Cell Nucleus / metabolism
Chromatin / metabolism
Cytoskeleton / metabolism
Gene Expression Profiling
Gene Expression Regulation, Developmental*
Genome-Wide Association Study
Genomics
HEK293 Cells
Humans
Mice
Muscle Development
MyoD Protein / metabolism*
Myoblasts / metabolism*
Phenotype
Promoter Regions, Genetic
Signal Transduction
Transcriptome
Transfection
Wnt Proteins / metabolism
alpha Catenin / metabolism*
beta Catenin / metabolism*
|
| IF |
5.763
|
| 引用数 |
2
|
| リソース情報 |
| 実験動物マウス |
RBRC06137 |
