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Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment

A normal endowment of nephrons in the mammalian kidney requires a balance of nephron progenitor self-renewal and differentiation throughout development. Here, we provide evidence for a novel action of ureteric branch tip-derived Wnt11 in progenitor cell organization and interactions within the nephr...

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Autores principales: O'Brien, Lori L, Combes, Alexander N, Short, Kieran M, Lindström, Nils O, Whitney, Peter H, Cullen-McEwen, Luise A, Ju, Adler, Abdelhalim, Ahmed, Michos, Odyssé, Bertram, John F, Smyth, Ian M, Little, Melissa H, McMahon, Andrew P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281319/
https://www.ncbi.nlm.nih.gov/pubmed/30516471
http://dx.doi.org/10.7554/eLife.40392
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author O'Brien, Lori L
Combes, Alexander N
Short, Kieran M
Lindström, Nils O
Whitney, Peter H
Cullen-McEwen, Luise A
Ju, Adler
Abdelhalim, Ahmed
Michos, Odyssé
Bertram, John F
Smyth, Ian M
Little, Melissa H
McMahon, Andrew P
author_facet O'Brien, Lori L
Combes, Alexander N
Short, Kieran M
Lindström, Nils O
Whitney, Peter H
Cullen-McEwen, Luise A
Ju, Adler
Abdelhalim, Ahmed
Michos, Odyssé
Bertram, John F
Smyth, Ian M
Little, Melissa H
McMahon, Andrew P
author_sort O'Brien, Lori L
collection PubMed
description A normal endowment of nephrons in the mammalian kidney requires a balance of nephron progenitor self-renewal and differentiation throughout development. Here, we provide evidence for a novel action of ureteric branch tip-derived Wnt11 in progenitor cell organization and interactions within the nephrogenic niche, ultimately determining nephron endowment. In Wnt11 mutants, nephron progenitors dispersed from their restricted niche, intermixing with interstitial progenitors. Nephron progenitor differentiation was accelerated, kidneys were significantly smaller, and the nephron progenitor pool was prematurely exhausted, halving the final nephron count. Interestingly, RNA-seq revealed no significant differences in gene expression. Live imaging of nephron progenitors showed that in the absence of Wnt11 they lose stable attachments to the ureteric branch tips, continuously detaching and reattaching. Further, the polarized distribution of several markers within nephron progenitors is disrupted. Together these data highlight the importance of Wnt11 signaling in directing nephron progenitor behavior which determines a normal nephrogenic program.
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spelling pubmed-62813192018-12-07 Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment O'Brien, Lori L Combes, Alexander N Short, Kieran M Lindström, Nils O Whitney, Peter H Cullen-McEwen, Luise A Ju, Adler Abdelhalim, Ahmed Michos, Odyssé Bertram, John F Smyth, Ian M Little, Melissa H McMahon, Andrew P eLife Developmental Biology A normal endowment of nephrons in the mammalian kidney requires a balance of nephron progenitor self-renewal and differentiation throughout development. Here, we provide evidence for a novel action of ureteric branch tip-derived Wnt11 in progenitor cell organization and interactions within the nephrogenic niche, ultimately determining nephron endowment. In Wnt11 mutants, nephron progenitors dispersed from their restricted niche, intermixing with interstitial progenitors. Nephron progenitor differentiation was accelerated, kidneys were significantly smaller, and the nephron progenitor pool was prematurely exhausted, halving the final nephron count. Interestingly, RNA-seq revealed no significant differences in gene expression. Live imaging of nephron progenitors showed that in the absence of Wnt11 they lose stable attachments to the ureteric branch tips, continuously detaching and reattaching. Further, the polarized distribution of several markers within nephron progenitors is disrupted. Together these data highlight the importance of Wnt11 signaling in directing nephron progenitor behavior which determines a normal nephrogenic program. eLife Sciences Publications, Ltd 2018-12-05 /pmc/articles/PMC6281319/ /pubmed/30516471 http://dx.doi.org/10.7554/eLife.40392 Text en © 2018, O'Brien et al http://creativecommons.org/licenses/by/4.0/ 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 Developmental Biology
O'Brien, Lori L
Combes, Alexander N
Short, Kieran M
Lindström, Nils O
Whitney, Peter H
Cullen-McEwen, Luise A
Ju, Adler
Abdelhalim, Ahmed
Michos, Odyssé
Bertram, John F
Smyth, Ian M
Little, Melissa H
McMahon, Andrew P
Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment
title Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment
title_full Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment
title_fullStr Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment
title_full_unstemmed Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment
title_short Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment
title_sort wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281319/
https://www.ncbi.nlm.nih.gov/pubmed/30516471
http://dx.doi.org/10.7554/eLife.40392
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