| Summary: | 博士 === 國立臺灣大學 === 生命科學系 === 105 === Focal adhesion kinase is known to mediate multiple vital cellular processes and be involved in embryogenesis and organ development. Despite its necessity, how FAK regulates and integrates with other cellular signals during early embryogenesis still remains poorly understood. Here, I first demonstrated the high sequence similarity of zebrafish fak1a and fak1b to human FAK. Using antisense morpholino (MO), I observed that the loss of Fak1a impaired epiboly, convergence and extension and hypoblast cell migration in a non cell-autonomous manner. Furthermore, I showed clear disturbance of the filamentous actin (F-actin) linkage bundles between actin-ring and yolk syncytial nuclei that appeared to affect epiboly in fak1a morphants. Genetic deletion of fak1a using CRISPR/Cas9 mediated gene editing reveals minor gastrulation defects than that of morphants, but some genes were induced both in morphants and mutants. It suggests that similar molecular pathways were affected. More importantly, I found that overexpression of fak1a or wnt5b mRNA could cross rescue convergence defects induced by wnt5b or fak1a MO, respectively. Both Wnt5b and Fak1a appeared to mediate gastrulation via Rac1 and Cdc42, since both small GTPases could synergistically rescue wnt5b and fak1a morphant phenotypes. Taken together, I demonstrate for the first time the missing functional interaction between Wnt and FAK signaling to mediate gastrulation cell movements via precise regulation of Rac1 and Cdc42 activities and subsequent actin dynamics.
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