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http://dx.doi.org/10.14348/molcells.2019.0140

Loss of βPix Causes Defects in Early Embryonic Development, and Cell Spreading and Platelet-Derived Growth Factor-Induced Chemotaxis in Mouse Embryonic Fibroblasts  

Kang, TaeIn (School of Biological Sciences, Seoul National University)
Lee, Seung Joon (Computational Biology & Genomics)
Kwon, Younghee (School of Biological Sciences, Seoul National University)
Park, Dongeun (School of Biological Sciences, Seoul National University)
Abstract
${\beta}Pix$ is a guanine nucleotide exchange factor for the Rho family small GTPases, Rac1 and Cdc42. It is known to regulate focal adhesion dynamics and cell migration. However, the in vivo role of ${\beta}Pix$ is currently not well understood. Here, we report the production and characterization of ${\beta}Pix$-KO mice. Loss of ${\beta}Pix$ results in embryonic lethality accompanied by abnormal developmental features, such as incomplete neural tube closure, impaired axial rotation, and failure of allantois-chorion fusion. We also generated ${\beta}Pix$-KO mouse embryonic fibroblasts (MEFs) to examine ${\beta}Pix$ function in mouse fibroblasts. ${\beta}Pix$-KO MEFs exhibit decreased Rac1 activity, and defects in cell spreading and platelet-derived growth factor (PDGF)-induced ruffle formation and chemotaxis. The average size of focal adhesions is increased in ${\beta}Pix$-KO MEFs. Interestingly, ${\beta}Pix$-KO MEFs showed increased motility in random migration and rapid wound healing with elevated levels of MLC2 phosphorylation. Taken together, our data demonstrate that ${\beta}Pix$ plays essential roles in early embryonic development, cell spreading, and cell migration in fibroblasts.
Keywords
${\beta}Pix$; cell motility; embryonic lethality; focal adhesion; mouse embryonic fibroblast;
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