title: The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium.
abstract: Epithelial morphogenesis and stability are essential for normal development and organ homeostasis. The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr. Here we show that the transition to a columnar epithelium fails in mutant embryos that lack the tumor suppressor PTEN, although proliferation, patterning and apical-basal polarity markers are normal in the mutants. The Pten phenotype is mimicked by constitutive activation of PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kinases AKT and mTORC1. High resolution imaging shows that PTEN is required for stabilization of planar cell packing in the neural plate and for the formation of stable apical-basal microtubule arrays. The data suggest that appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis.
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Grego-Bessa
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Joshua
authors.initials: J
authors.lastname: Bloomekatz
authors.affiliation: Human Oncology and Pathogenesis Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Pau
authors.initials: P
authors.lastname: Castel
authors.affiliation: Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Omelchenko
authors.affiliation: Human Oncology and Pathogenesis Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.|Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Anderson
mesh_terms: D000818:Animals; D004848:Epithelium / Q000196:embryology*; D055786:Gene Knockout Techniques; D051379:Mice; D054258:Neural Plate / Q000196:embryology*; D038081:Organogenesis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase
chemical_list: C000631433:Pdk1 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D017346:Protein Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: PI3 kinase; cell biology; developmental biology; epithelial morphogenesis; mouse; neural tube defect; stem cells; tumor suppressor
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