Roles of bone morphogenetic protein signaling and its antagonism in holoprosencephaly.
Roles of bone morphogenetic protein signaling and its antagonism in holoprosencephaly.
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DOI：
10.1002/ajmg.c.30256
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发表时间：
2010-02-15
影响因子：
3.1
通讯作者：
Anderson, Ryan M.
中科院分区：
文献类型：
--
作者：
Klingensmith, John;Matsui, Maiko;Yang, Yu-Ping;Anderson, Ryan M.
无前脑畸形(HPE)是最常见的前脑畸形，其原因是在神经管的吻端未能完全分隔左右半球。由于驱动头部发育的组织相互作用，这些前脑缺陷通常伴随着颅面结构的中线缺陷。建立头部组织前体的早期事件，以及这些组织之间后来的相互作用，对正常的头部形成至关重要。任何一种工艺中的缺陷都可能导致HPE。骨形态发生蛋白(BMPs)是一个分泌型细胞因子家族，在头部形成的早期阶段通常起着负面作用，因此必须在多种情况下加以减弱，以确保前脑和颅面的正常发育。Chordin和Noggin是BMP信号的内源性细胞外拮抗剂，促进前脑和面部的正常组织。这两种因子水平降低的小鼠突变体显示的突变表型与人类HPE序列中看到的畸形范围非常相似。Chordin和Noggin的部分作用是通过拮抗BMP信号对Sonic Hedgehog和Nodal通路的抑制作用，这两条通路的遗传损伤都与人类HPE有关。Chordin的研究；Noggin突变小鼠正在帮助我们了解HPE及其相关畸形的分子、细胞和遗传发病机制。
Holoprosencephaly (HPE) is the most common malformation of the forebrain, resulting from a failure to completely septate the left and right hemispheres at the rostral end of the neural tube. Because of the tissue interactions that drive head development, these forebrain defects are typically accompanied by midline deficiencies of craniofacial structures. Early events in setting up tissue precursors of the head, as well as later interactions between these tissues, are critical for normal head formation. Defects in either process can result in HPE. Signaling by Bone Morphogenetic Proteins (BMPs), a family of secreted cytokines, generally plays negative roles in early stages of head formation, and thus must be attenuated in multiple contexts to ensure proper forebrain and craniofacial development. Chordin and Noggin are endogenous, extracellular antagonists of BMP signaling that promote the normal organization of the forebrain and face. Mouse mutants with reduced levels of both factors display mutant phenotypes remarkably analogous to the range of malformations seen in human HPE sequence. Chordin and Noggin function in part by antagonizing the inhibitory effects of BMP signaling on the Sonic hedgehog and Nodal pathways, genetic lesions in each being associated with human HPE. Study of Chordin;Noggin mutant mice is helping us to understand the molecular, cellular and genetic pathogenesis of HPE and associated malformations.
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影响因子：
2.7
作者：
Petryk, A;Anderson, RM;O'Connor, MB
通讯作者：
O'Connor, MB
影响因子：
64.8
作者：
Ding, JX;Yang, L;Shen, MM
通讯作者：
Shen, MM
影响因子：
64.5
作者：
SASAI, Y;LU, B;DEROBERTIS, EM
通讯作者：
DEROBERTIS, EM
影响因子：
5.3
作者：
Cheng, Xun;Hsu, Ching-mei;Monuki, Edwin S.
通讯作者：
Monuki, Edwin S.
影响因子：
64.5
作者：
LIEM, KF;TREMML, G;JESSELL, TM
通讯作者：
JESSELL, TM