Positive regulation of myogenic bHLH factors and skeletal muscle development by the cell surface receptor CDO
Positive regulation of myogenic bHLH factors and skeletal muscle development by the cell surface receptor CDO
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DOI：
10.1016/j.devcel.2004.10.009
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发表时间：
2004-12-01
影响因子：
11.8
通讯作者：
Krauss, RS
中科院分区：
文献类型：
--
作者：
Cole, F;Zhang, W;Krauss, RS
骨骼肌发生受MyoD家族的bHLH转录因子控制，该家族与MEF-2因子沿着构成维持生肌转录程序的正反馈网络。肌肉前体之间的细胞-细胞接触促进了肌生成，但其潜在机制知之甚少。CDO是一种IG超家族成员，是细胞表面受体复合物的一种成分，存在于细胞-细胞接触部位，在体外积极调节肌生成。我们在这里报告，小鼠缺乏CDO显示延迟骨骼肌发育。此外，来自这些小鼠的卫星细胞在体外分化缺陷。CDO通过增强异源二聚体的形成来激活肌源性bHLH因子，最可能是通过诱导E蛋白的过度磷酸化。Cdo基因反过来又是MyoD的靶标。因此，细胞-细胞接触的促生肌作用与生肌bHLH因子的活性有关。此外，肌源性正反馈网络从细胞表面延伸到细胞核。
Skeletal myogenesis is controlled by bHLH transcription factors of the MyoD family that, along with MEF-2 factors, comprise a positive feedback network that maintains the myogenic transcriptional program. Cell-cell contact between muscle precursors promotes myogenesis, but little is known of the underlying mechanisms. CDO, an Ig superfamily member, is a component of a cell surface receptor complex found at sites of cell-cell contact that positively regulates myogenesis in vitro. We report here that mice lacking CDO display delayed skeletal muscle development. Additionally, satellite cells from these mice differentiate defectively in vitro. CDO functions to activate myogenic bHLH factors via enhanced heterodimer formation, most likely by inducing hyperphosphorylation of E proteins. The Cdo gene is, in turn, a target of MyoD. The promyogenic effect of cell-cell contact is therefore linked to the activity of myogenic bHLH factors. Furthermore, the myogenic positive feedback network extends from the cell surface to the nucleus.