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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10 November 2003
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November 10 2003
Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA
Krzysztof Kobielak,
Krzysztof Kobielak
Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
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H. Amalia Pasolli,
H. Amalia Pasolli
Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
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Laura Alonso,
Laura Alonso
Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
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Lisa Polak,
Lisa Polak
Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
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Elaine Fuchs
Elaine Fuchs
Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
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Krzysztof Kobielak
Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
H. Amalia Pasolli
Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
Laura Alonso
Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
Lisa Polak
Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
Elaine Fuchs
Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
Address correspondence to Elaine Fuchs, Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, 1230 York Ave., Box 300, The Rockefeller University, New York, NY 10021-6399. Tel.: (212) 327-7953. Fax: (212) 327-7954. email: [email protected]
Abbreviations used in this paper: DP, dermal papilla; DS, dermal sheath; IRS, inner root sheath; KO, knockout; ORS, outer root sheath; P, postnatal day; Shh, Sonic hedgehog WT, wild-type.
Received:
September 05 2003
Accepted:
October 01 2003
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2003
J Cell Biol (2003) 163 (3): 609–623.
Article history
Received:
September 05 2003
Accepted:
October 01 2003
Citation
Krzysztof Kobielak, H. Amalia Pasolli, Laura Alonso, Lisa Polak, Elaine Fuchs; Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA . J Cell Biol 10 November 2003; 163 (3): 609–623. doi: https://doi.org/10.1083/jcb.200309042
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