title: Differential sensitivity of epidermal cell subpopulations to beta-catenin-induced ectopic hair follicle formation.
abstract: Wnt signalling is required for hair follicle development and for the growth phase (anagen) of postnatal follicles. When the pathway is activated at high levels in adult mouse epidermis, ectopic follicles form from existing follicles, interfollicular epidermis (IFE) and sebaceous glands, revealing a remarkable ability of the tissue to be reprogrammed. To compare the competence of different epidermal cell populations to form ectopic follicles, we expressed a 4-hydroxy-tamoxifen (4OHT) inducible, stabilised beta-catenin transgene (DeltaNbeta-cateninER) under the control of two different promoters. We targeted the reservoir of stem cells in the hair follicle bulge via the keratin 15 (K15) promoter and targeted the sebaceous glands and base of the follicle (bulb) with a truncated K5 promoter (DeltaK5). No ectopic follicles formed in the IFE in either model, establishing the autonomy of the IFE stem cell compartment in undamaged epidermis. Activation of beta-catenin in the bulge stimulated proliferation and bulge expansion. Existing hair follicles entered anagen, but no ectopic follicles formed. DeltaK5DeltaNbeta-cateninER expressing hair follicles also entered anagen on 4OHT treatment. In addition, a subpopulation of cells at the base of the sebaceous gland readily formed ectopic follicles, resulting in complete and reversible conversion of sebaceous glands into hair follicles. Combined activation of beta-catenin and the vitamin D receptor enhanced differentiation of sebaceous gland-derived hair follicles and stimulated ectopic follicle formation in the hair follicle bulb, but not in the bulge. Our results suggest that the bulge and sebaceous gland are, respectively, non-permissive and permissive niches for Wnt induced hair follicle differentiation.
authors.affiliation: CRUK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Baker
authors.forename: Annemieke
authors.initials: A
authors.lastname: Verstuyf
authors.forename: Kim B
authors.initials: KB
authors.lastname: Jensen
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Watt
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin
references.citation: Cell Stem Cell. 2009 Jun 5;4(6):499-502
references.pmid: 19497277
references.citation: Development. 1999 Oct;126(20):4557-68
references.pmid: 10498690
references.citation: Proc Natl Acad Sci U S A. 2007 May 29;104(22):9428-33
references.pmid: 17517646
references.citation: Nature. 2008 Apr 3;452(7187):650-3
references.pmid: 18385740
references.citation: Cell. 1998 Nov 25;95(5):605-14
references.pmid: 9845363
references.citation: Cell. 2001 May 18;105(4):533-45
references.pmid: 11371349
references.citation: Genes Dev. 2005 Jul 1;19(13):1596-611
references.pmid: 15961525
references.citation: Curr Biol. 1998 Apr 23;8(9):516-24
references.pmid: 9560338
references.citation: J Bone Miner Res. 2010 May;25(5):1157-66
references.pmid: 19888899
references.citation: J Cell Sci. 2001 Oct;114(Pt 19):3419-31
references.pmid: 11682602
references.citation: Development. 2002 Jan;129(1):95-109
references.pmid: 11782404
references.citation: Nat Rev Cancer. 2003 Jun;3(6):444-51
references.pmid: 12778134
references.citation: J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):314-6
references.pmid: 20138991
references.citation: Genes Dev. 2001 Jul 1;15(13):1688-705
references.pmid: 11445543
references.citation: EMBO Mol Med. 2009 Aug;1(5):260-7
references.pmid: 20049729
references.citation: Nat Genet. 2008 Nov;40(11):1291-9
references.pmid: 18849992
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8551-6
references.pmid: 10411913
references.citation: Dev Cell. 2005 Jul;9(1):121-31
references.pmid: 15992546
references.citation: Cell Stem Cell. 2009 May 8;4(5):427-39
references.pmid: 19427292
references.citation: Cell Stem Cell. 2009 Feb 6;4(2):155-69
references.pmid: 19200804
references.citation: Nature. 2003 Mar 20;422(6929):317-22
references.pmid: 12646922
references.citation: Development. 2006 Nov;133(22):4427-38
references.pmid: 17035290
references.citation: J Biol Chem. 2002 Sep 6;277(36):33398-410
references.pmid: 12052822
references.citation: J Invest Dermatol. 2006 Jul;126(7):1459-68
references.pmid: 16778814
references.citation: Dev Cell. 2002 May;2(5):643-53
references.pmid: 12015971
references.citation: Nat Genet. 2009 Oct;41(10):1068-75
references.pmid: 19718027
references.citation: Nat Genet. 1999 Apr;21(4):410-3
references.pmid: 10192393
references.citation: Science. 2004 Jan 16;303(5656):359-63
references.pmid: 14671312
references.citation: J Invest Dermatol. 2003 Apr;120(4):501-11
references.pmid: 12648211
references.citation: Br J Dermatol. 1994 Sep;131(3):303-10
references.pmid: 7918003
references.citation: Stem Cells. 2006 Dec;24(12):2826-39
references.pmid: 16960130
references.citation: Genes Dev. 2003 May 15;17(10):1219-24
references.pmid: 12756226
references.citation: Cold Spring Harb Symp Quant Biol. 2008;73:333-50
references.pmid: 19022769
references.citation: PLoS One. 2008 Jan 23;3(1):e1483
references.pmid: 18213391
references.citation: Development. 2009 Oct;136(20):3505-14
references.pmid: 19783739
references.citation: J Invest Dermatol. 2003 Nov;121(5):963-8
references.pmid: 14708593
references.citation: Nat Med. 2005 Dec;11(12):1351-4
references.pmid: 16288281
references.citation: Nature. 2007 May 17;447(7142):316-20
references.pmid: 17507982
references.citation: Physiol Rev. 2001 Jan;81(1):449-494
references.pmid: 11152763
references.citation: Development. 2004 Apr;131(8):1787-99
references.pmid: 15084463
references.citation: Cold Spring Harb Symp Quant Biol. 2008;73:503-12
references.pmid: 19022747
references.citation: Science. 2010 Mar 12;327(5971):1385-9
references.pmid: 20223988
references.citation: EMBO Mol Med. 2010 Jan;2(1):16-25
references.pmid: 20043278
references.citation: Bioorg Med Chem Lett. 2002 Jun 17;12(12):1629-32
references.pmid: 12039578
references.citation: Eur J Histochem. 1998;42(2):121-32
references.pmid: 9728289
references.citation: Development. 2003 Nov;130(21):5241-55
references.pmid: 12954714
references.citation: J Invest Dermatol. 2008 Aug;128(8):2113-7
references.pmid: 18337835
references.citation: J Invest Dermatol. 2002 Feb;118(2):216-25
references.pmid: 11841536
references.citation: Cell Stem Cell. 2008 Jul 3;3(1):33-43
references.pmid: 18593557
references.citation: Biotechniques. 2004 Oct;37(4):610-3
references.pmid: 15517974
references.citation: Cell. 2006 Aug 11;126(3):597-609
references.pmid: 16901790
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10063-8
references.pmid: 17553962