Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm
Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm
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DOI：
10.1016/j.devcel.2005.09.011
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发表时间：
2005-11-01
影响因子：
11.8
通讯作者：
Matsuo, I
中科院分区：
文献类型：
--
作者：
Kimura-Yoshida, C;Nakano, H;Matsuo, I
小鼠胚胎轴最初形成为近端-远端方向，随后随着内脏内胚层细胞的定向迁移而转变为预期的前后（A-P）极性。重要的是，Otx2（一种同源盒基因）对于这一发育过程至关重要。然而，人们对控制轴转换的遗传调控机制知之甚少。在这里，由于 Otx2 缺陷导致的轴转换缺陷可以通过表达 Dkk1（一种 Wnt 拮抗剂）或去除一个 β-连环蛋白基因拷贝来挽救。典型 Wnt 配体的错误表达也会抑制正确的 A-P 轴旋转。此外，在 Otx2 缺陷和 Wnt 错误表达的内脏内胚层中，β-连环蛋白定位的不对称分布受到损害。同时，经典的 Wnt 和 Dkk1 在内脏内胚层细胞的迁移中分别充当排斥和吸引的引导信号。我们提出，Wnt/β-连环蛋白信号传导通过引导细胞向前原小鼠胚胎中的预期前部迁移来介导 A-P 轴极化。
The mouse embryonic axis is initially formed with a proximal-distal orientation followed by subsequent conversion to a prospective anterior-posterior (A-P) polarity with directional migration of visceral endoderm cells. Importantly, Otx2, a homeobox gene, is essential to this developmental process. However, the genetic regulatory mechanism governing axis conversion is poorly understood. Here, defective axis conversion due to Otx2 deficiency can be rescued by expression of Dkk1, a Wnt antagonist, or following removal of one copy of the beta-catenin gene. Misexpression of a canonical Wnt ligand can also inhibit correct A-P axis rotation. Moreover, asymmetrical distribution of beta-catenin localization is impaired in the Otx2-deficient and Wnt- misexpressing visceral endoderm. Concurrently, canonical Wnt and Dkk1 function as repulsive and attractive guidance cues, respectively, in the migration of visceral endoderm cells. We propose that Wnt/beta-catenin signaling mediates A-P axis polarization by guiding cell migration toward the prospective anterior in the pregastrula mouse embryo.