The mammalian twisted gastrulation gene functions in foregut and craniofacial development
The mammalian twisted gastrulation gene functions in foregut and craniofacial development
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DOI：
10.1016/j.ydbio.2003.11.015
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发表时间：
2004-03-15
影响因子：
2.7
通讯作者：
O'Connor, MB
中科院分区：
文献类型：
--
作者：
Petryk, A;Anderson, RM;O'Connor, MB
细胞-细胞信号的细胞外调节器控制着生物体发育的许多方面。扭曲原肠形成(Twsg1)基因产物是一种小的、分泌丰富的半胱氨酸蛋白，具有独特的特性，能够以上下文依赖的方式增强或抑制骨形态发生蛋白(BMP)亚家族的转化生长因子-β(TGF-β)信号。在这份报告中，我们描述了与Twsg1功能丧失相关的早期胚胎和骨骼表型。所有Twsg1突变小鼠，无论遗传背景如何，都表现出颈椎神经弓的缺失。在C57BL/6背景下，我们还观察到明显的前脑缺陷，包括吻部截断、全前脑畸形、旋视，以及第一鳃弓(BA1)的改变，导致颌骨缺失(失智症)。标记物表达的特征表明，这些缺陷可归因于来自前脑组织中心的信号丢失，包括来自前神经脊(ANR)的Fgf8和来自前脊板(PrCP)的Shh。此外，我们发现前肠内胚层存在缺陷，Hex表达减少，这可能是导致前脑和BA1缺陷的原因之一。(C)2003 Elsevier Inc.保留所有权利。
Extracellular modulators of cell-cell signaling control numerous aspects of organismal development. The Twisted gastrulation (Twsg1) gene product is a small, secreted cysteine-rich protein that has the unusual property of being able to either enhance or inhibit signaling by the bone morphogenetic protein (BMP) subfamily of TGF-beta type factors in a context-dependent manner. In this report, we characterize the early embryonic and skeletal phenotypes associated with loss of Twsg1 function in mice. All Twsg1 mutant mice, irrespective of genetic background, exhibit deletions of neural arches in the cervical vertebrae. In a C57BL/6 background, we also observe pronounced forebrain defects including rostral truncations, holoprosencephaly, cyclopia, as well as alterations in the first branchial arch (BA1) leading to lack of jaw (agnathia). Characterization of marker expression suggests that these defects are attributable to loss of signaling from forebrain-organizing centers including Fgf8 from the anterior neural ridge (ANR) and Shh from the prechordal plate (PrCP). In addition, we find defects in the foregut endoderm and a reduction in Hex expression, which may contribute to both the forebrain and BA1 defects. (C) 2003 Elsevier Inc. All rights reserved.