Loss of AP-2α impacts multiple aspects of ventral body wall development and closure
Loss of AP-2α impacts multiple aspects of ventral body wall development and closure
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DOI：
10.1016/j.ydbio.2003.11.021
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发表时间：
2004-03-15
影响因子：
2.7
通讯作者：
Williams, T
中科院分区：
文献类型：
--
作者：
Brewer, S;Williams, T
涉及腹侧体壁的人类出生缺陷是常见的，但对哺乳动物体壁闭合的机制知之甚少。AP-2 α转录因子敲除小鼠提供了一个特殊的工具来理解这种特殊的病理，因为它有一个最严重的腹体壁闭合缺陷，胸腹裂。为了深入了解负责体壁闭合的复杂形态学事件，我们研究了AP-2 α基因敲除小鼠的发育过程。参与正常腹体壁闭合的几种组织在缺乏AP-2 α的情况下是有缺陷的，包括与初级体壁、脐环和次级体壁的中胚层相关的组织。这些缺陷，加上AP-2 α的表达模式，表明AP-2 α参与多种发育机制，指导腹体壁的形态发生，包括细胞迁移，分化和死亡。在脐环处，体襞的迁移和融合失败，腹带和腹侧肌肉组织的形成和迁移也失败。此外，脐环处的细胞沉积机制受到干扰。因此，体壁的中胚层隔室不发达。我们还认为，AP-2 α是必要的信号从表面外胚层底层中胚层适当的发展和关闭腹体壁。这些发现提供了对AP-2 α在腹侧体壁闭合中如何发挥作用的基本理解，并提供了对相关人类出生缺陷的深入了解。(C)2004年爱思唯尔公司All rights reserved.
Human birth defects involving the ventral body wall are common, yet little is known about the mechanism of body wall closure in mammals. The AP-2alpha transcription factor knock-out mouse provides an exceptional tool to understand this particular pathology, since it has one of the most severe ventral body wall closure defects, thoracoabdominoschisis. To gain insight into the complex morphological events responsible for body wall closure, we have studied this developmental process in AP-2alpha knock-out mice. Several tissues involved in normal ventral body wall closure are defective in the absence of AP-2alpha, including those associated with the primary body wall, the umbilical ring, and the mesoderm of the secondary body wall. These defects, coupled with the expression pattern of AP-2alpha, suggest that AP-2alpha is involved in multiple developmental mechanisms directing the morphogenesis of the ventral body wall, including cell migration, differentiation, and death. There is a failure of migration and fusion of the body folds at the umbilical ring, as well as in the formation and migration of the abdominal bands and ventral musculature. Furthermore, the mechanism of cell deposition at the umbilical ring is disturbed. Consequently, the mesodermal compartment of the body wall is underdeveloped. We also suggest that AP-2alpha is required for signaling from the surface ectoderm to the underlying mesoderm for proper development and closure of the ventral body wall. These findings provide a fundamental understanding of how AP-2alpha functions in the closure of the ventral body wall, as well as offer insight into related human birth defects. (C) 2004 Elsevier Inc. All rights reserved.