Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse
Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse
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DOI：
10.1016/s1534-5807(01)00041-7
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发表时间：
2001-09-01
影响因子：
11.8
通讯作者：
Westphal, H
中科院分区：
文献类型：
--
作者：
Mukhopadhyay, M;Shtrom, S;Westphal, H
Dickkopf1(Dkk1)是一种分泌型蛋白，作为Wnt抑制剂，与BMP抑制剂一起，能够诱导非洲爪哇异位头部的形成。在这里，我们发现Dkk1缺失突变胚胎缺乏位于中脑前部的头部结构。对嵌合胚胎的分析表明，Dkk1在前中轴中胚层中是必需的，但在前内脏内胚层中不需要。此外，突变胚胎显示出肢体手指的复制和融合。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都发挥着作用。我们的数据为在胚胎模式形成过程中需要分泌的Wnt拮抗剂提供了直接的遗传学证据，并暗示Dkk1在前部规范过程中是一个重要的诱导物，在远端肢体模式过程中也是一个调节因素。
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.