A critical role for sonic hedgehog signaling in the early expansion of the developing brain
A critical role for sonic hedgehog signaling in the early expansion of the developing brain
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DOI：
10.1038/nn797
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发表时间：
2002-02-01
影响因子：
25
通讯作者：
Keynes, R
中科院分区：
文献类型：
--
作者：
Britto, J;Tannahill, D;Keynes, R
在发育过程中协调脊椎动物大脑三维形状的机制在很大程度上是未知的。我们发现，在发育中的中脑和前脑早期囊泡快速、广泛扩张的过程中，音hedgehog基因（Shh）起着至关重要的作用。脊索从中脑底板的短暂移位导致囊泡异常折叠和整体塌陷，并伴有中脑细胞增殖减少和细胞死亡增加。同时，脊索和底板的Shh表达在局部减少，而明显的模式和分化正常进行。sh -分泌细胞以剂量依赖的方式植入小鼠，恢复正常的中脑扩张；相反，在环巴胺拮抗Shh信号通路后，扩张被阻滞。我们的研究结果表明，来自腹侧中线的Shh信号对于调节早期发育过程中的大脑形态发生至关重要。
The mechanisms that coordinate the three-dimensional shape of the vertebrate brain during development are largely unknown. We have found that sonic hedgehog (Shh) is crucial in driving the rapid, extensive expansion of the early vesicles of the developing midbrain and forebrain. Transient displacement of the notochord from the midbrain floor plate resulted in abnormal folding and overall collapse of the vesicles, accompanied by reduced cell proliferation and increased cell death in the midbrain. Simultaneously, expression of Shh decreased locally in the notochord and floor plate, whereas overt patterning and differentiation proceeded normally. Normal midbrain expansion was restored by implantation of Shh-secreting cells in a dose-dependent manner; conversely, expansion was retarded following antagonism of the Shh signaling pathway by cyclopamine. Our results indicate that Shh signaling from the ventral midline is essential for regulating brain morphogenesis during early development.