cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes
cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes
复制标题
DOI：
10.1038/nature01973
复制
发表时间：
2003-09-18
期刊：
影响因子：
64.8
通讯作者：
Zon, LI
中科院分区：
文献类型：
--
作者：
Davidson, AJ;Ernst, P;Zon, LI
器官发生依赖于胚胎内不同细胞类型的形成。hox基因对这一过程很重要，据信它赋予细胞沿前后轴沿着的位置同一性（1-3）。在这里，我们已经确定了尾相关基因cdx 4的位点突变kugelig（kgg），斑马鱼突变与造血早期缺陷，这是与异常的前后图案和异常的hox基因表达。kgg胚胎中的血液缺陷可以通过过表达hoxb 7a或hoxa 9a而不是hoxb 8a来挽救，这表明造血缺陷是由特定hox基因的扰动引起的。此外，在kgg突变体中造血缺陷不能被scl过度表达所挽救，这表明cdx 4和hox基因的作用是使后中胚层有能力进行血液发育。斑马鱼发育过程中或小鼠胚胎干细胞中cdx 4的过表达诱导血液形成并改变hox基因的表达。综上所述，这些发现表明cdx 4调控hox基因，是脊椎动物胚胎发生过程中造血细胞命运的规范所必需的。
Organogenesis is dependent on the formation of distinct cell types within the embryo. Important to this process are the hox genes, which are believed to confer positional identities to cells along the anteroposterior axis(1-3). Here, we have identified the caudal-related gene cdx4 as the locus mutated in kugelig (kgg), a zebrafish mutant with an early defect in haematopoiesis that is associated with abnormal anteroposterior patterning and aberrant hox gene expression. The blood deficiency in kgg embryos can be rescued by overexpressing hoxb7a or hoxa9a but not hoxb8a, indicating that the haematopoietic defect results from perturbations in specific hox genes. Furthermore, the haematopoietic defect in kgg mutants is not rescued by scl overexpression, suggesting that cdx4 and hox genes act to make the posterior mesoderm competent for blood development. Overexpression of cdx4 during zebrafish development or in mouse embryonic stem cells induces blood formation and alters hox gene expression. Taken together, these findings demonstrate that cdx4 regulates hox genes and is necessary for the specification of haematopoietic cell fate during vertebrate embryogenesis.