Sonic hedgehog-dependent synthesis of laminin α1 controls basement membrane assembly in the myotome
Sonic hedgehog-dependent synthesis of laminin α1 controls basement membrane assembly in the myotome
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DOI：
10.1242/dev.036087
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发表时间：
2009-10-15
期刊：
影响因子：
4.6
通讯作者：
Borycki, Anne-Gaelle
中科院分区：
文献类型：
--
作者：
Anderson, Claire;Thorsteinsdottir, Solveig;Borycki, Anne-Gaelle
在胚胎发育过程中，基底膜在组织形态发生中具有重要的结构和信号作用，但控制其形成的机制仍然知之甚少。层粘连蛋白是基底膜的关键成分，被认为是启动基底膜组装所必需的。在这里，我们报告了在没有Sonic Hedgehog(Shh)信号的情况下，肌节内的肌祖细胞在腹侧体节内异常迁移，我们认为这一缺陷是由于未能形成肌瘤基底膜。我们发现，在Shh(-/-)胚胎中，编码层粘连蛋白α1的Lama1的表达不被激活。恢复Lama1的表达或将外源层粘连蛋白-111添加到Shh(-/-)；Gli3(-/-)胚胎恢复肌瘤基底膜，表明层粘连蛋白-111是启动肌瘤基底膜组装的必要条件和充分条件。这项研究揭示了Shh信号在控制层粘连蛋白-111的合成和启动肌节基底膜组装中的重要作用。此外，我们的数据表明，层粘连蛋白-111的功能不能被层粘连蛋白-511所补偿。
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 alpha 1, 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.