IGFs, insulin, Shh, bFGF, and TGF-β1 interact synergistically to promote somite myogenesis in vitro
IGFs, insulin, Shh, bFGF, and TGF-β1 interact synergistically to promote somite myogenesis in vitro
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DOI：
10.1006/dbio.2000.9784
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发表时间：
2000-08-15
影响因子：
2.7
通讯作者：
Hauschka, SD
中科院分区：
文献类型：
--
作者：
Pirskanen, A;Kiefer, JC;Hauschka, SD
本课题组和其他研究人员的研究表明，体外体节肌发生受神经管和脊索因子调节，包括Wnt、Sonic Hedgehog(Shh)、碱性成纤维细胞生长因子(BFGF)和转化生长因子-β1(TGF-β1)。在这项研究中，我们报道了胰岛素和胰岛素样生长因子I和II(IGF-I和IGF-II)也促进了含有单个体节或体节大小的中胚片的外植体培养的肌肉发生，并且胰岛素/IGFS与bFGF和转化生长因子-β1的组合促进了更高水平的肌肉发生。我们还发现，在这个体外系统中，Shh促进了肌肉生成，Shh与胰岛素/IGFS协同作用，促进了高水平的肌肉生成。RT-PCR分析在神经管和体节中均检测到胰岛素、IGF-II、胰岛素受体和IGF受体mRNAs，而在整个胚胎中检测到IGF-I转录本，但在神经管或体节中未检测到。用抗胰岛素、抗IGF-II、抗胰岛素受体或抗IGF受体阻断抗体处理体节-神经管共培养细胞，可显著减少肌发生。这些结果与系统的IGF-I以及神经管分泌的胰岛素和IGF-II在胚胎发育过程中作为额外的早期肌源性信号的假设是一致的。进一步研究表明，胰岛素、胰岛素样生长因子、碱性成纤维细胞生长因子和Shh也能刺激体节细胞增殖并影响细胞凋亡。(C)2000年学术出版社。
Studies from our group and others have shown that in vitro somite myogenesis is regulated by neural tube and notochord factors including Wnt, Sonic hedgehog (Shh), and basic fibroblast growth factor (bFGF) together with transforming growth factor-beta 1 (TGF-beta 1). In this study we report that insulin and insulin-like growth factors I and II (IGF-I and -II) also promote myogenesis in explant cultures containing single somites or somite-sized pieces of segmental plate mesoderm from 2-day (stage 10-14) chicken embryos and that the combination of insulin/IGFs with bFGF plus TGF-beta 1 promotes even higher levels of myogenesis. We also found that Shh promotes myogenesis in this in vitro system and that Shh interacts synergistically with insulin/IGFs to promote high levels of myogenesis. RT-PCR analysis detected insulin, IGF-II, insulin receptor, and IGF receptor mRNAs in both the neural tube and the somites, whereas IGF-I transcripts were detected in entire embryos but not in the neural tube or somites. Treatment of somite-neural tube cocultures with anti-insulin, anti-IGF-II, anti-insulin receptor, or anti-IGF receptor blocking antibodies caused a significant decrease in myogenesis. These results are consistent with the hypothesis that systemic IGF-I as well as insulin and IGF-II secreted by the neural tube act as additional early myogenic signals during embryogenesis. Further studies indicate that insulin, IGFs, bFGF, and Shh also stimulate somite cell proliferation and influence apoptosis. (C) 2000 Academic Press.