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Critical roles of type III phosphatidylinositol phosphate kinase in murine embryonic visceral endoderm and adult intestine.

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This publication describes a study in which the PtdIns3P 5-kinase, PIPKIII (also known as PIKfyve and Fab1), is ablated. The whole body knock-out mice die around E8.5. The authors find profound defects in the embryonic visceral endoderm, an epithelial cell layer which provides nutrients to the growing embryo. These observations led the authors to generate an intestinal epithelia-specific knock-out line in order to test epithelial polarization and function in a well-characterized cell type. The resultant mice show dramatic defects in the morphology and membrane trafficking within the intestinal epithelia. Moreover, the intestinal dysfunction leads to early death and a phenotype with properties that are similar to Crohn's disease. In addition, the authors add to a growing body of literature that PIPKIII/Pikfyve is the sole source of PtdIns(3,5)P(2). Moreover, the intestinal epithelia joins a growing list of tissues affected by impaired PIPKIII function. The list includes the nervous system, heart, lung, kidney and spleen. The ability to generate additional lines in which PIPKIII/Pikfyve is conditionally ablated promises to expand knowledge of the roles of this signaling lipid in these and other tissues. This review was also published on F1000Prime at

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