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

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 mu...

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Autores principales: Grego-Bessa, Joaquim, Bloomekatz, Joshua, Castel, Pau, Omelchenko, Tatiana, Baselga, José, Anderson, Kathryn V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739759/
https://www.ncbi.nlm.nih.gov/pubmed/26809587
http://dx.doi.org/10.7554/eLife.12034
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author Grego-Bessa, Joaquim
Bloomekatz, Joshua
Castel, Pau
Omelchenko, Tatiana
Baselga, José
Anderson, Kathryn V
author_facet Grego-Bessa, Joaquim
Bloomekatz, Joshua
Castel, Pau
Omelchenko, Tatiana
Baselga, José
Anderson, Kathryn V
author_sort Grego-Bessa, Joaquim
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.12034.001
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spelling pubmed-47397592016-02-04 The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium Grego-Bessa, Joaquim Bloomekatz, Joshua Castel, Pau Omelchenko, Tatiana Baselga, José Anderson, Kathryn V eLife Cell Biology 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. DOI: http://dx.doi.org/10.7554/eLife.12034.001 eLife Sciences Publications, Ltd 2016-01-26 /pmc/articles/PMC4739759/ /pubmed/26809587 http://dx.doi.org/10.7554/eLife.12034 Text en © 2015, Grego-Bessa et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Grego-Bessa, Joaquim
Bloomekatz, Joshua
Castel, Pau
Omelchenko, Tatiana
Baselga, José
Anderson, Kathryn V
The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium
title The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium
title_full The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium
title_fullStr The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium
title_full_unstemmed The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium
title_short The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium
title_sort tumor suppressor pten and the pdk1 kinase regulate formation of the columnar neural epithelium
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739759/
https://www.ncbi.nlm.nih.gov/pubmed/26809587
http://dx.doi.org/10.7554/eLife.12034
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