Anderson Claire, Thorsteinsdóttir Sólveig, Borycki Anne-Gaëlle
Department of Biomedical Science, University of Sheffield, Sheffield, UK.
Development. 2009 Oct;136(20):3495-504. doi: 10.1242/dev.036087.
Basement membranes have essential structural and signalling roles in tissue morphogenesis during embryonic development, but the mechanisms that control their formation are still poorly understood. Laminins are key components of basement membranes and are thought to be essential for initiation of basement membrane assembly. Here, we report that muscle progenitor cells populating the myotome migrate aberrantly in the ventral somite in the absence of sonic hedgehog (Shh) signalling, and we show that this defect is due to the failure to form a myotomal basement membrane. We reveal that expression of Lama1, which encodes laminin alpha1, a subunit of laminin-111, is not activated in Shh(-/-) embryos. Recovery of Lama1 expression or addition of exogenous laminin-111 to Shh(-/-);Gli3(-/-) embryos restores the myotomal basement membrane, demonstrating that laminin-111 is necessary and sufficient to initiate assembly of the myotomal basement membrane. This study uncovers an essential role for Shh signalling in the control of laminin-111 synthesis and in the initiation of basement membrane assembly in the myotome. Furthermore, our data indicate that laminin-111 function cannot be compensated by laminin-511.
基底膜在胚胎发育过程中的组织形态发生中具有重要的结构和信号传导作用，但控制其形成的机制仍知之甚少。层粘连蛋白是基底膜的关键成分，被认为是基底膜组装起始所必需的。在此，我们报告在缺乏音猬因子（Shh）信号传导的情况下，定位于肌节的肌肉祖细胞在腹侧体节中异常迁移，并且我们表明这种缺陷是由于未能形成肌节基底膜所致。我们发现，编码层粘连蛋白α1（层粘连蛋白-111的一个亚基）的Lama1在Shh基因敲除（Shh(-/-)）胚胎中未被激活。恢复Lama1表达或向Shh(-/-);Gli3(-/-)胚胎添加外源性层粘连蛋白-111可恢复肌节基底膜，表明层粘连蛋白-111对于启动肌节基底膜的组装是必要且充分的。本研究揭示了Shh信号传导在控制层粘连蛋白-111合成以及在肌节基底膜组装起始中的重要作用。此外，我们的数据表明层粘连蛋白-111的功能不能由层粘连蛋白-511补偿。
