Dkk1 and Wnt3 interact to control head morphogenesis in the mouse
Dkk1 and Wnt3 interact to control head morphogenesis in the mouse
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DOI：
10.1242/dev.018853
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发表时间：
2008-05-15
期刊：
影响因子：
4.6
通讯作者：
Tam, Patrick P. L.
中科院分区：
文献类型：
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作者：
Lewis, Samara L.;Khoo, Poh-Lynn;Tam, Patrick P. L.
Dkk 1的缺失导致前胚层组织中的异位WNT/β-连环蛋白信号传导活性，并损害小鼠原肠胚内胚层中的细胞运动。Dkk 1和Wnt 3的表达结构域的并列表明拮抗剂-激动剂相互作用。当Wnt 3活性降低时Dkk 1的下调揭示了调节WNT信号传导的反馈机制。化合物DKK 1; Wnt 3杂合突变体胚胎表现出头部截短和躯干畸形，这在Dkk 1（+/-）或Wnt 3（+/-）胚胎中均未发现。减少Dkk 1（-/-）胚胎中Wnt 3基因的剂量部分挽救了截短的头部表型。这些发现强调头部发育对WNT 3信号传导水平敏感，并且DKK 1是在前部形态发生期间调节WNT 3活性的关键拮抗剂。
Loss of Dkk1 results in ectopic WNT/beta-catenin signalling activity in the anterior germ layer tissues and impairs cell movement in the endoderm of the mouse gastrula. The juxtaposition of the expression domains of Dkk1 and Wnt3 is suggestive of an antagonist-agonist interaction. The downregulation of Dkk1 when Wnt3 activity is reduced reveals a feedback mechanism for regulating WNT signalling. Compound Dkk1; Wnt3 heterozygous mutant embryos display head truncation and trunk malformation, which are not found in either Dkk1(+/-) or Wnt3(+/-) embryos. Reducing the dose of Wnt3 gene in Dkk1(-/-) embryos partially rescues the truncated head phenotype. These findings highlight that head development is sensitive to the level of WNT3 signalling and that DKK1 is the key antagonist that modulates WNT3 activity during anterior morphogenesis.