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Cell Tissue Res 2020 Sep 01;3813:493-508. doi: 10.1007/s00441-020-03237-2.
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Disabled-2: a positive regulator of the early differentiation of myoblasts.

Shang N , Lee JTY , Huang T , Wang C , Lee TL , Mok SC , Zhao H , Chan WY .

Dab2 is an adaptor protein and a tumor suppressor. Our previous study has found that Dab2 was expressed in early differentiating skeletal muscles in mouse embryos. In this study, we determined the role of Dab2 in the skeletal muscle differentiation using C2C12 myoblasts in vitro and Xenopus laevis embryos in vivo. The expression of Dab2 was increased in C2C12 myoblasts during the formation of myotubes in vitro. Knockdown of Dab2 expression in C2C12 myoblasts resulted in a reduction of myotube formation, whereas the myotube formation was enhanced upon overexpression of Dab2. Re-expression of Dab2 in C2C12 myoblasts with downregulated expression of Dab2 restored their capacity to form myotubes. Microarray profiling and subsequent network analyses on the 155 differentially expressed genes after Dab2 knockdown showed that Mef2c was an important myogenic transcription factor regulated by Dab2 through the p38 MAPK pathway. It was also involved in other pathways that are associated with muscular development and functions. In Xenopus embryos developed in vivo, XDab2 was expressed in the myotome of somites where various myogenic markers were also expressed. Knockdown of XDab2 expression with antisense morpholinos downregulated the expression of myogenic markers in somites. In conclusion, this study is the first to provide solid evidence to show that Dab2 is a positive regulator of the early myoblast differentiation.

PubMed ID: 32607799
PMC ID: PMC7431403
Article link: Cell Tissue Res
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: acta4 actn4 cdh11 dab2 etv1 gapdh hdac9 igf2 itga6 klf4 lama2 mapk1 mapk14 mef2c mef2d myf5 myh1 myh3 myh4 myh6 myl4 myod1 myos nhs pappa pax3 pax7 pdgfb
Morpholinos: dab2 MO3 dab2 MO4

Phenotypes: Xla.wt + dab2 MO (Fig. 9 b-l)

Article Images: [+] show captions
References [+] :
Alfaro, sFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial repair. 2011, Pubmed