Dickkopf1对于小鼠胚胎头部诱导和肢体形态发生是必需的。

Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse.

作者信息

Mukhopadhyay M, Shtrom S, Rodriguez-Esteban C, Chen L, Tsukui T, Gomer L, Dorward D W, Glinka A, Grinberg A, Huang S P, Niehrs C, Izpisúa Belmonte J C, Westphal H

机构信息

Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Dev Cell. 2001 Sep;1(3):423-34. doi: 10.1016/s1534-5807(01)00041-7.

DOI:10.1016/s1534-5807(01)00041-7

PMID:11702953

Abstract

Dickkopf1 (Dkk1) is a secreted protein that acts as a Wnt inhibitor and, together with BMP inhibitors, is able to induce the formation of ectopic heads in Xenopus. Here, we show that Dkk1 null mutant embryos lack head structures anterior of the midbrain. Analysis of chimeric embryos implicates the requirement of Dkk1 in anterior axial mesendoderm but not in anterior visceral endoderm for head induction. In addition, mutant embryos show duplications and fusions of limb digits. Characterization of the limb phenotype strongly suggests a role for Dkk1 both in cell proliferation and in programmed cell death. Our data provide direct genetic evidence for the requirement of secreted Wnt antagonists during embryonic patterning and implicate Dkk1 as an essential inducer during anterior specification as well as a regulator during distal limb patterning.

摘要

Dickkopf1（Dkk1）是一种分泌蛋白，作为Wnt抑制剂，与骨形态发生蛋白（BMP）抑制剂一起，能够在非洲爪蟾中诱导异位头部的形成。在此，我们表明Dkk1基因敲除突变体胚胎在中脑前方缺乏头部结构。对嵌合胚胎的分析表明，在头部诱导过程中，Dkk1在前轴中胚层而非前脏内胚层中是必需的。此外，突变体胚胎表现出肢体指（趾）的重复和融合。肢体表型的特征强烈表明Dkk1在细胞增殖和程序性细胞死亡中均发挥作用。我们的数据为胚胎模式形成过程中分泌型Wnt拮抗剂的需求提供了直接的遗传学证据，并表明Dkk1是前侧特化过程中的必需诱导因子以及远端肢体模式形成过程中的调节因子。