Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis
Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis
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DOI：
10.1016/j.ydbio.2008.11.022
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发表时间：
2009-03-01
影响因子：
2.7
通讯作者：
Motoyama, Jun
中科院分区：
文献类型：
--
作者：
Aoto, Kazushi;Shikata, Yayoi;Motoyama, Jun
在人类中，前脑无裂畸形（HPE）是一种常见的出生缺陷，其特征是大脑，面部和口腔结构缺乏中线细胞。为了了解HPE的病因，我们研究了哺乳动物前索板（PrCP）细胞参与HPE的发病机制和分泌蛋白音刺猬（Shh）在PrCP发展的要求。我们使用大鼠PrCP病变实验和Dil标记，PrCP细胞是必不可少的中线发育的前脑，前肠内胚层，和腹侧颅中胚层在哺乳动物。我们证明，PrCP细胞不发育成腹侧颅中胚层Shh（-/-）胚胎。使用Shh（-/-）和嵌合体胚胎，我们表明Shh信号是以非细胞自主方式维持PrCP细胞所必需的。此外，在PrCP发育过程中通常出现以促进中线组织的hedgehog（HH）反应细胞在Shh信号传导不存在的情况下不会发育。这表明PrCP细胞分泌的Shh蛋白诱导HH应答细胞分化为中线细胞。在本研究中，我们表明，维持一个可行的人口PrCP细胞的Shh信号是一个重要的过程中的发展中线的大脑和颅面结构。这些发现为动态脑和颅面形态发生过程中HPE的发病机制提供了新的见解。(C)2008年爱思唯尔公司All rights reserved.
In humans, holoprosencephaly (HPE) is a common birth defect characterized by the absence of midline cells from brain, facial, and oral structures. To understand the pathoetiology of HPE, we investigated the involvement of mammalian prechordal plate (PrCP) cells in HPE pathogenesis and the requirement of the secreted protein sonic hedgehog (Shh) in PrCP development. We show using rat PrCP lesion experiments and Dil labeling that PrCP cells are essential for midline development of the forebrain, foregut endoderm, and ventral cranial mesoderm in mammals. We demonstrate that PrCP cells do not develop into ventral cranial mesoderm in Shh(-/-) embryos. Using Shh(-/-) and chimeric embryos we show that Shh signal is required for the maintenance of PrCP cells in a non-cell autonomous manner. In addition, the hedgehog (HH)-responding cells that normally appear during PrCP development to contribute to midline tissues, do not develop in the absence of Shh signaling. This suggests that Shh protein secreted from PrCP cells induces the differentiation of HH-responding cells into midline cells. In the present study, we show that the maintenance of a viable population of PrCP cells by Shh signal is an essential process in development of the midline of the brain and craniofacial structures. These findings provide new insight into the mechanism underlying HPE pathoetiology during dynamic brain and craniofacial morphogenesis. (C) 2008 Elsevier Inc. All rights reserved.