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The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium

Authors: Grego Bessa, Joaquim; Bloomekatz, Joshua; Castel Morales, Pau; Omelchenko, Tatiana; Baselga Torres, Josep, 1959-; Anderson, Kathryn V.;

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.

Keywords

tumor suppressor, QH301-705.5, Science, Organogenesis, Homeòstasi, Protein Serine-Threonine Kinases, neural tube defect, Epithelium, Gene Knockout Techniques, Mice, PI3 kinase, Morphogenesis, Homeostasis, Animals, Biology (General), Neural Plate, Q, R, Morfogènesi, PTEN Phosphohydrolase, epithelial morphogenesis, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, Cell Biology, Medicine

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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