Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Development. 2024 Oct 1;151(19). doi: 10.1242/dev.202597. Epub 2024 Sep 30.
Pharyngeal endoderm cells undergo convergence and extension (C&E), which is essential for endoderm pouch formation and craniofacial development. Our previous work implicates Gα13/RhoA-mediated signaling in regulating this process, but the underlying mechanisms remain unclear. Here, we have used endoderm-specific transgenic and Gα13 mutant zebrafish to demonstrate that Gα13 plays a crucial role in pharyngeal endoderm C&E by regulating RhoA activation and E-cadherin expression. We showed that during C&E, endodermal cells gradually establish stable cell-cell contacts, acquire apical-basal polarity and undergo actomyosin-driven apical constriction, which are processes that require Gα13. Additionally, we found that Gα13-deficient embryos exhibit reduced E-cadherin expression, partially contributing to endoderm C&E defects. Notably, interfering with RhoA function disrupts spatial actomyosin activation without affecting E-cadherin expression. Collectively, our findings identify crucial cellular processes for pharyngeal endoderm C&E and reveal that Gα13 controls this through two independent pathways - modulating RhoA activation and regulating E-cadherin expression - thus unveiling intricate mechanisms governing pharyngeal endoderm morphogenesis.
咽内胚层细胞经历汇聚延伸(C&E),这对于内胚层囊形成和颅面发育至关重要。我们之前的工作表明 Gα13/RhoA 介导的信号在调节这个过程中起作用,但潜在的机制仍不清楚。在这里,我们使用内胚层特异性转基因和 Gα13 突变体斑马鱼来证明 Gα13 通过调节 RhoA 激活和 E-钙黏蛋白表达在咽内胚层 C&E 中发挥关键作用。我们表明,在 C&E 过程中,内胚层细胞逐渐建立稳定的细胞-细胞接触,获得顶-基底极性,并经历肌动球蛋白驱动的顶端收缩,这些过程需要 Gα13。此外,我们发现 Gα13 缺陷型胚胎表现出 E-钙黏蛋白表达减少,这部分导致内胚层 C&E 缺陷。值得注意的是,干扰 RhoA 功能会破坏空间肌动球蛋白激活,而不影响 E-钙黏蛋白表达。总之,我们的研究结果确定了咽内胚层 C&E 的关键细胞过程,并表明 Gα13 通过两种独立途径来控制这一过程,即调节 RhoA 激活和调节 E-钙黏蛋白表达,从而揭示了调节咽内胚层形态发生的复杂机制。