Growth of limb muscle is dependent on skeletal-derived Indian hedgehog.
Growth of limb muscle is dependent on skeletal-derived Indian hedgehog.
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DOI：
10.1016/j.ydbio.2011.06.002
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发表时间：
2011-08-15
影响因子：
2.7
通讯作者：
Olwin BB
中科院分区：
文献类型：
--
作者：
Bren-Mattison Y;Hausburg M;Olwin BB
在胚胎发生过程中，肌肉和骨骼在时间和空间上非常接近地发育。我们发现，印度刺猬，骨源性信号分子，参与骨骼肌的生长。在Ihh−/−胚胎中，骨骼肌发育在胚胎第14.5天出现异常，在胚胎第20.5天出现后肢肌肉的急剧损失。为了进一步研究Ihh在肌发生中的作用，我们操纵了发育中的鸡后肢中的Ihh表达。鸡胚胎后肢中Ihh的减少减少了骨骼肌质量，与Ihh−/−小鼠胚胎中观察到的相似。肌肉质量的减少似乎是Ihh的直接作用，因为通过RCAS逆转录病毒感染鸡胚后肢异位表达Ihh恢复肌肉质量。这些作用与骨长度无关，并且在Shh不表达时发生，表明Ihh直接作用于胎儿成肌细胞以调节次级肌发生。Ihh基因敲除小鼠胚胎中肌肉质量的损失伴随着成肌细胞凋亡的急剧增加，并伴随着p21蛋白的损失。我们的数据表明，IHH促进胎儿成肌细胞的生存分化成二级肌纤维，通过维持p21蛋白水平。
During embryogenesis, muscle and bone develop in close temporal and spatial proximity. We show that Indian Hedgehog, a bone-derived signaling molecule, participates in growth of skeletal muscle. In Ihh−/− embryos, skeletal muscle development appears abnormal at embryonic day 14.5 and at later ages through embryonic day 20.5, dramatic losses of hindlimb muscle occur. To further examine the role of Ihh in myogenesis, we manipulated Ihh expression in the developing chick hindlimb. Reduction of Ihh in chicken embryo hindlimbs reduced skeletal muscle mass similar to that seen in Ihh−/− mouse embryos. The reduction in muscle mass appears to be a direct effect of Ihh since ectopic expression of Ihh by RCAS retroviral infection of chicken embryo hindlimbs restores muscle mass. These effects are independent of bone length, and occur when Shh is not expressed, suggesting Ihh acts directly on fetal myoblasts to regulate secondary myogenesis. Loss of muscle mass in Ihh null mouse embryos is accompanied by a dramatic increase in myoblast apoptosis accompanied by a loss of p21 protein. Our data suggest that Ihh promotes fetal myoblast survival during their differentiation into secondary myofibers by maintaining p21 protein levels.
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BUTLER, J;COSMOS, E;BRIERLEY, J
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