He Fenglei, Xiong Wei, Yu Xueyan, Espinoza-Lewis Ramon, Liu Chao, Gu Shuping, Nishita Michiru, Suzuki Kentaro, Yamada Gen, Minami Yasuhiro, Chen Yiping
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Development. 2008 Dec;135(23):3871-9. doi: 10.1242/dev.025767. Epub 2008 Oct 23.
Tissue and molecular heterogeneities are present in the developing secondary palate along the anteroposterior (AP) axis in mice. Here, we show that Wnt5a and its receptor Ror2 are expressed in a graded manner along the AP axis of the palate. Wnt5a deficiency leads to a complete cleft of the secondary palate, which exhibits distinct phenotypic alterations at histological, cellular and molecular levels in the anterior and posterior regions of the palate. We demonstrate that there is directional cell migration within the developing palate. In the absence of Wnt5a, this directional cell migration does not occur. Genetic studies and in vitro organ culture assays further demonstrate a role for Ror2 in mediating Wnt5a signaling in the regulation of cell proliferation and migration during palate development. Our results reveal distinct regulatory roles for Wnt5a in gene expression and cell proliferation along the AP axis of the developing palate, and an essential role for Wnt5a in the regulation of directional cell migration.
在小鼠发育中的次生腭沿前后轴存在组织和分子异质性。在此，我们表明Wnt5a及其受体Ror2沿腭的前后轴呈梯度表达。Wnt5a缺陷导致次生腭完全裂开，在腭的前部和后部区域的组织学、细胞和分子水平上表现出明显的表型改变。我们证明在发育中的腭内存在定向细胞迁移。在缺乏Wnt5a的情况下，这种定向细胞迁移不会发生。遗传学研究和体外器官培养试验进一步证明Ror2在腭发育过程中调节细胞增殖和迁移的Wnt5a信号传导中起作用。我们的结果揭示了Wnt5a在发育中腭的前后轴上基因表达和细胞增殖中的不同调节作用，以及Wnt5a在定向细胞迁移调节中的重要作用。
