Wnt5b integrates Fak1a to mediate gastrulation cell movements via Rac1 and Cdc42
Open Access
- 26 February 2020
- journal article
- research article
- Published by The Royal Society in Open Biology
- Vol. 10 (2), 190273
- https://doi.org/10.1098/rsob.190273
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.Keywords
Funding Information
- Ministry of Science and Technology, Taiwan (NSC96-2311-B-002-023-MY3, NSC98-2311-B-002-006-MY3, NSC99-2320-B-002-079-MY3)
- National Taiwan University (Long-Term Research Grant-10R70821, NTU CESRP-10R70602A5, NTU ERP-10R80600)
This publication has 87 references indexed in Scilit:
- FLASH assembly of TALENs for high-throughput genome editingNature Biotechnology, 2012
- Focal adhesion kinase is essential for cardiac looping and multichamber heart formationgenesis, 2010
- Binding of APC and dishevelled mediates Wnt5a-regulated focal adhesion dynamics in migrating cellsThe EMBO Journal, 2010
- Regulation of convergence and extension movements during vertebrate gastrulation by the Wnt/PCP pathwaySeminars in Cell & Developmental Biology, 2009
- Identification of common and unique modifiers of zebrafish midline bifurcation and cyclopiaDevelopmental Biology, 2009
- Back and forth between cell fate specification and movement during vertebrate gastrulationCurrent Opinion in Genetics & Development, 2008
- Nuclear FAK Promotes Cell Proliferation and Survival through FERM-Enhanced p53 DegradationMolecular Cell, 2008
- FAK–Src signalling through paxillin, ERK and MLCK regulates adhesion disassemblyNature, 2004
- Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient miceNature, 1995
- Stages of embryonic development of the zebrafishDevelopmental Dynamics, 1995