PUBLICATION

Wnt5b integrates Fak1a to mediate gastrulation cell movements via Rac1 and Cdc42

Authors
Hung, I.C., Chen, T.M., Lin, J.P., Tai, Y.L., Shen, T.L., Lee, S.J.
ID
ZDB-PUB-200226-12
Date
2020
Source
Open Biology   10: 190273 (Journal)
Registered Authors
Lee, Shyh-Jye
Keywords
FAK, Wnt, actin, cell migration, convergent extension, gastrulation
MeSH Terms
  • Actins
  • Animals
  • CRISPR-Cas Systems
  • Cell Line
  • Cell Movement
  • Focal Adhesion Kinase 1/genetics*
  • Focal Adhesion Kinase 1/metabolism
  • Gastrulation
  • Mice
  • Mutation
  • Signal Transduction
  • Wnt-5a Protein/genetics
  • Wnt-5a Protein/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • cdc42 GTP-Binding Protein/genetics
  • cdc42 GTP-Binding Protein/metabolism*
  • rac1 GTP-Binding Protein/genetics
  • rac1 GTP-Binding Protein/metabolism*
PubMed
32097584 Full text @ Open Biol.
Abstract
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.
Errata / Notes
This article is corrected by ZDB-PUB-220906-198 .
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