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Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA

Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, L...

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Autores principales: Kobielak, Krzysztof, Pasolli, H. Amalia, Alonso, Laura, Polak, Lisa, Fuchs, Elaine
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173651/
https://www.ncbi.nlm.nih.gov/pubmed/14610062
http://dx.doi.org/10.1083/jcb.200309042
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author Kobielak, Krzysztof
Pasolli, H. Amalia
Alonso, Laura
Polak, Lisa
Fuchs, Elaine
author_facet Kobielak, Krzysztof
Pasolli, H. Amalia
Alonso, Laura
Polak, Lisa
Fuchs, Elaine
author_sort Kobielak, Krzysztof
collection PubMed
description Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/β-catenin–regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated β-catenin. This places the block downstream from Lef1 expression but upstream from β-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized β-catenin to activate the hair specific keratin genes and generate the hair shaft.
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spelling pubmed-21736512008-05-01 Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA Kobielak, Krzysztof Pasolli, H. Amalia Alonso, Laura Polak, Lisa Fuchs, Elaine J Cell Biol Article Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/β-catenin–regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated β-catenin. This places the block downstream from Lef1 expression but upstream from β-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized β-catenin to activate the hair specific keratin genes and generate the hair shaft. The Rockefeller University Press 2003-11-10 /pmc/articles/PMC2173651/ /pubmed/14610062 http://dx.doi.org/10.1083/jcb.200309042 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Kobielak, Krzysztof
Pasolli, H. Amalia
Alonso, Laura
Polak, Lisa
Fuchs, Elaine
Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA
title Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA
title_full Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA
title_fullStr Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA
title_full_unstemmed Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA
title_short Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA
title_sort defining bmp functions in the hair follicle by conditional ablation of bmp receptor ia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173651/
https://www.ncbi.nlm.nih.gov/pubmed/14610062
http://dx.doi.org/10.1083/jcb.200309042
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