Focal adhesion kinase (FAK) mediates vital cellular pathways during development. Despite its necessity, how FAK regulates and integrates with other signals during early embryogenesis remains poorly understood. We found that the loss of Fak1a impaired epiboly, convergent extension and hypoblast cell migration in zebrafish embryos. We also observed a clear disturbance in cortical actin at the blastoderm margin and distribution of yolk syncytial nuclei. In addition, we investigated a possible link between Fak1a and a well-known gastrulation regulator, Wnt5b, and revealed that the overexpression of fak1a or wnt5b could cross-rescue convergence defects induced by a wnt5b or fak1a antisense morpholino (MO), respectively. Wnt5b and Fak1a were shown to converge in regulating Rac1 and Cdc42, which could synergistically rescue wnt5b and fak1a morphant phenotypes. Furthermore, we generated several alleles of fak1a mutants using CRISPR/Cas9, but those mutants only revealed mild gastrulation defects. However, injection of a subthreshold level of the wnt5b MO induced severe gastrulation defects in fak1a mutants, which suggested that the upregulated expression of wnt5b might complement the loss of Fak1a. Collectively, we demonstrated that a functional interaction between Wnt and FAK signalling mediates gastrulation cell movements via the possible regulation of Rac1 and Cdc42 and subsequent actin dynamics.

中文翻译：

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Wnt5b集成了Fak1a，以通过Rac1和Cdc42介导胃泌素细胞的运动。

黏着斑激酶（FAK）在发育过程中介导重要的细胞途径。尽管有必要，FAK在早期胚胎发生过程中如何调节并与其他信号整合仍知之甚少。我们发现，Fak1a的缺失削弱了斑马鱼胚胎中的外延，会聚延伸和次胚细胞迁移。我们还观察到在胚盘边缘和卵黄合胞核分布的皮层肌动蛋白明显紊乱。此外，我们研究了Fak1a与著名的胃调节因子Wnt5b之间的可能联系，并揭示了fak1a或wnt5b的过表达可能分别挽救wnt5b或fak1a反义吗啉代（MO）诱导的收敛缺陷。Wnt5b和Fak1a被证明在调节Rac1和Cdc42方面趋同，可以协同拯救wnt5b和fak1a形态表型。此外，我们使用CRISPR / Cas9生成了fak1a突变体的多个等位基因，但这些突变体仅显示出轻度的胃泌尿缺陷。但是，低于阈值水平的wnt5b MO注射会在fak1a突变体中引起严重的胃溃疡缺陷，这表明wnt5b的表达上调可能弥补了Fak1a的缺失。集体，我们证明Wnt和FAK信号之间的功能性相互作用通过Rac1和Cdc42的可能调节以及随后的肌动蛋白动力学介导了胃泌素细胞的运动。低于阈值水平的wnt5b MO注射会导致fak1a突变体出现严重的胃溃疡缺陷，这表明wnt5b的表达上调可能弥补了Fak1a的缺失。集体，我们证明Wnt和FAK信号之间的功能性相互作用通过Rac1和Cdc42的可能调节以及随后的肌动蛋白动力学介导了胃泌素细胞的运动。低于阈值水平的wnt5b MO注射会导致fak1a突变体出现严重的胃溃疡缺陷，这表明wnt5b的表达上调可能弥补了Fak1a的缺失。集体，我们证明Wnt和FAK信号之间的功能性相互作用通过Rac1和Cdc42的可能调节以及随后的肌动蛋白动力学介导了胃泌素细胞的运动。