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XB-ART-43229
Mol Biol Cell July 1, 2011; 22 (13): 2409-21.

Focal adhesion kinase protein regulates Wnt3a gene expression to control cell fate specification in the developing neural plate.

Fonar Y , Gutkovich YE , Root H , Malyarova A , Aamar E , Golubovskaya VM , Elias S , Elkouby YM , Frank D .


Abstract
Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase protein localized to regions called focal adhesions, which are contact points between cells and the extracellular matrix. FAK protein acts as a scaffold to transfer adhesion-dependent and growth factor signals into the cell. Increased FAK expression is linked to aggressive metastatic and invasive tumors. However, little is known about its normal embryonic function. FAK protein knockdown during early Xenopus laevis development anteriorizes the embryo. Morphant embryos express increased levels of anterior neural markers, with reciprocally reduced posterior neural marker expression. Posterior neural plate folding and convergence-extension is also inhibited. This anteriorized phenotype resembles that of embryos knocked down zygotically for canonical Wnt signaling. FAK and Wnt3a genes are both expressed in the neural plate, and Wnt3a expression is FAK dependent. Ectopic Wnt expression rescues this FAK morphant anteriorized phenotype. Wnt3a thus acts downstream of FAK to balance anterior-posterior cell fate specification in the developing neural plate. Wnt3a gene expression is also FAK dependent in human breast cancer cells, suggesting that this FAK-Wnt linkage is highly conserved. This unique observation connects the FAK- and Wnt-signaling pathways, both of which act to promote cancer when aberrantly activated in mammalian cells.

PubMed ID: 21551070
PMC ID: PMC3128541
Article link: Mol Biol Cell

Genes referenced: actl6a dkk1 eef1a2 egr2 en2 foxd1 foxd3 gbx2.1 gbx2.2 hesx1 hoxa2 hoxb3 hoxb9 hoxd1 meis3 ncam1 neurod1 otx2 ptk2 snai2 tub tubb2b wnt3 wnt3a wnt7a wnt8a
Morpholinos: ptk2 MO1 ptk2 MO2 ptk2 MO3 wnt3a MO1 wnt3a MO2 wnt3a MO3


Article Images: [+] show captions
References [+] :
Aamar, Xenopus Meis3 protein forms a hindbrain-inducing center by activating FGF/MAP kinase and PCP pathways. 2003, Pubmed, Xenbase


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