Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine.

The Lkb1 tumour suppressor is a multitasking kinase participating in a range of physiological processes. We have determined the impact of Lkb1 deficiency on intestinal homeostasis, particularly focussing on secretory cell differentiation and development since we observe strong expression of Lkb1 in...

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Autores principales:	Boris Y Shorning, Joanna Zabkiewicz, Afshan McCarthy, Helen B Pearson, Douglas J Winton, Owen J Sansom, Alan Ashworth, Alan R Clarke
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c739ed6499b44c68bdd144cb7ac93e19
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spelling	oai:doaj.org-article:c739ed6499b44c68bdd144cb7ac93e192021-12-02T20:12:17ZLkb1 deficiency alters goblet and paneth cell differentiation in the small intestine.1932-620310.1371/journal.pone.0004264https://doaj.org/article/c739ed6499b44c68bdd144cb7ac93e192009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19165340/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The Lkb1 tumour suppressor is a multitasking kinase participating in a range of physiological processes. We have determined the impact of Lkb1 deficiency on intestinal homeostasis, particularly focussing on secretory cell differentiation and development since we observe strong expression of Lkb1 in normal small intestine Paneth and goblet cells. We crossed mice bearing an Lkb1 allele flanked with LoxP sites with those carrying a Cyp1a1-specific inducible Cre recombinase. Lkb1 was efficiently deleted from the epithelial cells of the mouse intestine after intraperitoneal injection of the inducing agent beta-naphthoflavone. Bi-allelic loss of Lkb1 led to the perturbed development of Paneth and goblet cell lineages. These changes were characterised by the lack of Delta ligand expression in Lkb1-deficient secretory cells and a significant increase in the levels of the downstream Notch signalling effector Hes5 but not Hes1. Our data show that Lkb1 is required for the normal differentiation of secretory cell lineages within the intestine, and that Lkb1 deficiency modulates Notch signalling modulation in post-mitotic cells.Boris Y ShorningJoanna ZabkiewiczAfshan McCarthyHelen B PearsonDouglas J WintonOwen J SansomAlan AshworthAlan R ClarkePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 1, p e4264 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Boris Y Shorning Joanna Zabkiewicz Afshan McCarthy Helen B Pearson Douglas J Winton Owen J Sansom Alan Ashworth Alan R Clarke Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine.
description	The Lkb1 tumour suppressor is a multitasking kinase participating in a range of physiological processes. We have determined the impact of Lkb1 deficiency on intestinal homeostasis, particularly focussing on secretory cell differentiation and development since we observe strong expression of Lkb1 in normal small intestine Paneth and goblet cells. We crossed mice bearing an Lkb1 allele flanked with LoxP sites with those carrying a Cyp1a1-specific inducible Cre recombinase. Lkb1 was efficiently deleted from the epithelial cells of the mouse intestine after intraperitoneal injection of the inducing agent beta-naphthoflavone. Bi-allelic loss of Lkb1 led to the perturbed development of Paneth and goblet cell lineages. These changes were characterised by the lack of Delta ligand expression in Lkb1-deficient secretory cells and a significant increase in the levels of the downstream Notch signalling effector Hes5 but not Hes1. Our data show that Lkb1 is required for the normal differentiation of secretory cell lineages within the intestine, and that Lkb1 deficiency modulates Notch signalling modulation in post-mitotic cells.
format	article
author	Boris Y Shorning Joanna Zabkiewicz Afshan McCarthy Helen B Pearson Douglas J Winton Owen J Sansom Alan Ashworth Alan R Clarke
author_facet	Boris Y Shorning Joanna Zabkiewicz Afshan McCarthy Helen B Pearson Douglas J Winton Owen J Sansom Alan Ashworth Alan R Clarke
author_sort	Boris Y Shorning
title	Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine.
title_short	Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine.
title_full	Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine.
title_fullStr	Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine.
title_full_unstemmed	Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine.
title_sort	lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/c739ed6499b44c68bdd144cb7ac93e19
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Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine.

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