Defining BMP Functions in the Hair Follicle by Conditional Ablation of BMP Receptor IA

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2003 Nov 12

PMID 14610062

Citations 130

Authors

Krzysztof Kobielak

H Amalia Pasolli

Laura Alonso

Lisa Polak

Elaine Fuchs

Affiliations

Soon will be listed here.

Abstract

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/beta-catenin-regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated beta-catenin. This places the block downstream from Lef1 expression but upstream from beta-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 beta-catenin to activate the hair specific keratin genes and generate the hair shaft.

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References

Balciunaite G, Keller M, Balciunaite E, Piali L, Zuklys S, Mathieu Y . Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice. Nat Immunol. 2002; 3(11):1102-8. DOI: 10.1038/ni850. View

Oguin W, Sun T, Manabe M . Interaction of trichohyalin with intermediate filaments: three immunologically defined stages of trichohyalin maturation. J Invest Dermatol. 1992; 98(1):24-32. DOI: 10.1111/1523-1747.ep12494172. View

Botchkarev V . Bone morphogenetic proteins and their antagonists in skin and hair follicle biology. J Invest Dermatol. 2003; 120(1):36-47. DOI: 10.1046/j.1523-1747.2003.12002.x. View

Barrow J, Thomas K, Boussadia-Zahui O, Moore R, Kemler R, Capecchi M . Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge. Genes Dev. 2003; 17(3):394-409. PMC: 195987. DOI: 10.1101/gad.1044903. View

Nemer G, Nemer M . Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6. Dev Biol. 2003; 254(1):131-48. DOI: 10.1016/s0012-1606(02)00026-x. View

Yamashiro T, Aberg T, Levanon D, Groner Y, Thesleff I . Expression of Runx1, -2 and -3 during tooth, palate and craniofacial bone development. Gene Expr Patterns. 2003; 2(1-2):109-12. DOI: 10.1016/s0925-4773(02)00298-8. View

Jamora C, DasGupta R, Kocieniewski P, Fuchs E . Links between signal transduction, transcription and adhesion in epithelial bud development. Nature. 2003; 422(6929):317-22. PMC: 2424170. DOI: 10.1038/nature01458. View

Oro A, Higgins K . Hair cycle regulation of Hedgehog signal reception. Dev Biol. 2003; 255(2):238-48. DOI: 10.1016/s0012-1606(02)00042-8. View

Alonso L, Fuchs E . Stem cells in the skin: waste not, Wnt not. Genes Dev. 2003; 17(10):1189-200. DOI: 10.1101/gad.1086903. View

10.

Peterkin T, Gibson A, Patient R . GATA-6 maintains BMP-4 and Nkx2 expression during cardiomyocyte precursor maturation. EMBO J. 2003; 22(16):4260-73. PMC: 175790. DOI: 10.1093/emboj/cdg400. View

11.

Soshnikova N, Zechner D, Huelsken J, Mishina Y, Behringer R, Taketo M . Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb. Genes Dev. 2003; 17(16):1963-8. PMC: 196251. DOI: 10.1101/gad.263003. View

12.

Kaufman C, Zhou P, Pasolli H, Rendl M, Bolotin D, Lim K . GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev. 2003; 17(17):2108-22. PMC: 196453. DOI: 10.1101/gad.1115203. View

13.

Hardy M . The secret life of the hair follicle. Trends Genet. 1992; 8(2):55-61. DOI: 10.1016/0168-9525(92)90350-d. View

14.

Blessing M, Nanney L, King L, Jones C, Hogan B . Transgenic mice as a model to study the role of TGF-beta-related molecules in hair follicles. Genes Dev. 1993; 7(2):204-15. DOI: 10.1101/gad.7.2.204. View

15.

Schaeren-Wiemers N . A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-labelled cRNA probes. Histochemistry. 1993; 100(6):431-40. DOI: 10.1007/BF00267823. View

16.

Handjiski B, Eichmuller S, Hofmann U, Czarnetzki B, Paus R . Alkaline phosphatase activity and localization during the murine hair cycle. Br J Dermatol. 1994; 131(3):303-10. DOI: 10.1111/j.1365-2133.1994.tb08515.x. View

17.

Byrne C, Tainsky M, Fuchs E . Programming gene expression in developing epidermis. Development. 1994; 120(9):2369-83. DOI: 10.1242/dev.120.9.2369. View

18.

van Genderen C, Okamura R, Farinas I, Quo R, Parslow T, Bruhn L . Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev. 1994; 8(22):2691-703. DOI: 10.1101/gad.8.22.2691. View

19.

Nehls M, Pfeifer D, Schorpp M, Hedrich H, Boehm T . New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature. 1994; 372(6501):103-7. DOI: 10.1038/372103a0. View

20.

Zhou P, Byrne C, Jacobs J, Fuchs E . Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate. Genes Dev. 1995; 9(6):700-13. DOI: 10.1101/gad.9.6.700. View