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调节 WNT 信号活性是胚胎头部形成的关键。

Modulation of WNT signaling activity is key to the formation of the embryonic head.

机构信息

Embryology Unit, Children's Medical Research Institute, University of Sydney, Westmead, Australia.

出版信息

Cell Cycle. 2012 Jan 1;11(1):26-32. doi: 10.4161/cc.11.1.18700.

Abstract

The formation of the embryonic head begins with the assembly of the progenitor tissues of the brain, the head and face primordia and the foregut that are derived from the primary germ layers during gastrulation. Specification of the anterior-posterior polarity of major body parts and the morphogenesis of the head and brain specifically is driven by inductive signals including those mediated by BMP, Nodal, FGF and WNT. A critical role of β-catenin dependent WNT signalling activity for head morphogenesis has been revealed through the analysis of the phenotypic impact of loss of function mutation of an antagonist: DKK1, a transcriptional repressor: GSC; and the outcome of interaction of Dkk1 with genes coding three components of the canonical signalling pathway: the ligand WNT3, the co-receptor LRP6 and the transcriptional co-factor, β-catenin. The findings highlight the requirement of a stringent control of the timing, domain and level of canonical WNT signalling activity for the formation of the embryonic head.

摘要

胚胎头部的形成始于脑、头面原基和前肠的祖细胞组织的组装,这些组织是在原肠胚形成过程中由初级胚层衍生而来的。主要身体部位的前后极性的特化和头部和大脑的形态发生是由诱导信号驱动的,包括由 BMP、Nodal、FGF 和 WNT 介导的信号。通过分析拮抗剂 DKK1、转录抑制因子 GSC 的功能丧失突变的表型影响,以及 Dkk1 与编码经典信号通路三个组成部分的基因的相互作用的结果:配体 WNT3、共受体 LRP6 和转录共因子β-catenin,揭示了β-catenin 依赖性 WNT 信号活性对头部形态发生的关键作用。这些发现强调了严格控制经典 WNT 信号活性的时间、域和水平对头颈部形成的必要性。

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