STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo

Significance Striatin-interacting phosphatases and kinases (STRIPAK) complexes can regulate the cytoskeleton and cell migration in cell lines, but their roles in vivo in mammals are not known. Here, we show that mouse embryos that lack striatin-interacting protein 1 (STRIP1), a core component of STRIPAK complexes, arrest at midgestation with striking morphological defects. Strip1 mutants lack a trunk, and both paraxial and axial mesoderm fail to elongate along the anterior–posterior body axis. Mesodermal cells from Strip1 mutants have defects in actin organization, focal adhesions, and cell migration that can account for the failure of normal mesoderm migration. The findings demonstrate that STRIPAK is a critical regulator of mammalian cell migration and is likely to have important roles in tumor progression as well as development. Regulated mesoderm migration is necessary for the proper morphogenesis and organ formation during embryonic development. Cell migration and its dependence on the cytoskeleton and signaling machines have been studied extensively in cultured cells; in contrast, remarkably little is known about the mechanisms that regulate mesoderm cell migration in vivo. Here, we report the identification and characterization of a mouse mutation in striatin-interacting protein 1 (Strip1) that disrupts migration of the mesoderm after the gastrulation epithelial-to-mesenchymal transition (EMT). STRIP1 is a core component of the biochemically defined mammalian striatin-interacting phosphatases and kinase (STRIPAK) complexes that appear to act through regulation of protein phosphatase 2A (PP2A), but their functions in mammals in vivo have not been examined. Strip1-null mutants arrest development at midgestation with profound disruptions in the organization of the mesoderm and its derivatives, including a complete failure of the anterior extension of axial mesoderm. Analysis of cultured mesoderm explants and mouse embryonic fibroblasts from null mutants shows that the mesoderm migration defect is correlated with decreased cell spreading, abnormal focal adhesions, changes in the organization of the actin cytoskeleton, and decreased velocity of cell migration. The results show that STRIPAK complexes are essential for cell migration and tissue morphogenesis in vivo.

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