title: Cyclic expression of lhx2 regulates hair formation.
abstract: Hair is important for thermoregulation, physical protection, sensory activity, seasonal camouflage, and social interactions. Hair is generated in hair follicles (HFs) and, following morphogenesis, HFs undergo cyclic phases of active growth (anagen), regression (catagen), and inactivity (telogen) throughout life. The transcriptional regulation of this process is not well understood. We show that the transcription factor Lhx2 is expressed in cells of the outer root sheath and a subpopulation of matrix cells during both morphogenesis and anagen. As the HFs enter telogen, expression becomes undetectable and reappears prior to initiation of anagen in the secondary hair germ. In contrast to previously published results, we find that Lhx2 is primarily expressed by precursor cells outside of the bulge region where the HF stem cells are located. This developmental, stage- and cell-specific expression suggests that Lhx2 regulates the generation and regeneration of hair. In support of this hypothesis, we show that Lhx2 is required for anagen progression and HF morphogenesis. Moreover, transgenic expression of Lhx2 in postnatal HFs is sufficient to induce anagen. Thus, our results reveal an alternative interpretation of Lhx2 function in HFs compared to previously published results, since Lhx2 is periodically expressed, primarily in precursor cells distinct from those in the bulge region, and is an essential positive regulator of hair formation.
authors.affiliation: Umeå Center for Molecular Medicine, Umeå University, Umeå, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Törnqvist
authors.forename: Anna
authors.initials: A
authors.lastname: Sandberg
authors.forename: Anna-Carin
authors.initials: AC
authors.lastname: Hägglund
authors.forename: Leif
authors.initials: L
authors.lastname: Carlsson
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D006197:Hair / Q000196:embryology / Q000254:growth & development*; D018859:Hair Follicle / Q000254:growth & development; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors
references.citation: Development. 1997 Aug;124(15):2935-44
references.pmid: 9247336
references.citation: Development. 2006 Mar;133(6):1045-57
references.pmid: 16481354
references.citation: Development. 2004 Nov;131(21):5319-26
references.pmid: 15456728
references.citation: Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):227-31
references.pmid: 7678338
references.citation: Neuron. 2001 Nov 20;32(4):591-604
references.pmid: 11719201
references.citation: J Biol Chem. 2002 May 17;277(20):17901-5
references.pmid: 11834740
references.citation: Histochemistry. 1993 Dec;100(6):431-40
references.pmid: 7512949
references.citation: Development. 2005 Sep;132(18):4143-54
references.pmid: 16107474
references.citation: Trends Genet. 1992 Feb;8(2):55-61
references.pmid: 1566372
references.citation: J Invest Dermatol. 2000 May;114(5):901-8
references.pmid: 10771469
references.citation: Nat Cell Biol. 1999 Jul;1(3):158-64
references.pmid: 10559902
references.citation: J Invest Dermatol. 1999 Oct;113(4):523-32
references.pmid: 10504436
references.citation: Curr Biol. 1998 Sep 24;8(19):1058-68
references.pmid: 9768360
references.citation: Curr Opin Cell Biol. 2002 Dec;14(6):692-9
references.pmid: 12473341
references.citation: Dev Biol. 2007 Dec 15;312(2):484-500
references.pmid: 17991461
references.citation: Acta Neuropathol. 1992;84(6):581-7
references.pmid: 1471468
references.citation: FASEB J. 2001 Oct;15(12):2205-14
references.pmid: 11641247
references.citation: PLoS One. 2008 Apr 23;3(4):e2025
references.pmid: 18431502
references.citation: Nature. 2008 Jan 17;451(7176):340-4
references.pmid: 18202659
references.citation: Dev Cell. 2001 Jul;1(1):13-25
references.pmid: 11703920
references.citation: Cell. 1994 Sep 23;78(6):1017-25
references.pmid: 7923352
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2165-70
references.pmid: 10051612
references.citation: J Invest Dermatol. 2001 Jul;117(1):3-15
references.pmid: 11442744
references.citation: Nat Genet. 2008 Nov;40(11):1291-9
references.pmid: 18849992
references.citation: Genes Dev. 2003 May 15;17(10):1189-200
references.pmid: 12756224
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8551-6
references.pmid: 10411913
references.citation: J Invest Dermatol. 1993 Jul;101(1 Suppl):90S-97S
references.pmid: 8326158
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: Science. 2008 Jan 18;319(5861):304-9
references.pmid: 18202285
references.citation: Dev Biol. 2002 Apr 15;244(2):305-18
references.pmid: 11944939
references.citation: J Invest Dermatol. 2003 Apr;120(4):501-11
references.pmid: 12648211
references.citation: Science. 2006 Jun 30;312(5782):1946-9
references.pmid: 16809539
references.citation: J Exp Zool B Mol Dev Evol. 2003 Aug 15;298(1):164-80
references.pmid: 12949776
references.citation: Cell. 1990 Jun 29;61(7):1329-37
references.pmid: 2364430
references.citation: Cell. 2001 May 18;105(4):533-45
references.pmid: 11371349
references.citation: J Invest Dermatol. 1999 Apr;112(4):470-5
references.pmid: 10201531
references.citation: Trends Cell Biol. 1997 Nov;7(11):442-6
references.pmid: 17709003
references.citation: Genes Dev. 2005 Jul 1;19(13):1596-611
references.pmid: 15961525
references.citation: Trends Genet. 2000 Feb;16(2):75-83
references.pmid: 10652534
references.citation: Gene Expr Patterns. 2004 Sep;4(5):521-8
references.pmid: 15261829
references.citation: Physiol Rev. 2001 Jan;81(1):449-494
references.pmid: 11152763
references.citation: J Invest Dermatol. 1991 May;96(5):77S-78S
references.pmid: 2022884
references.citation: J Anat. 1952 Oct;86(4):342-56
references.pmid: 12999638
references.citation: Development. 2009 Apr;136(8):1375-85
references.pmid: 19304889
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16549-54
references.pmid: 15536133
references.citation: Dev Biol. 1999 Apr 15;208(2):281-92
references.pmid: 10191045
references.citation: J Cell Sci. 2001 Oct;114(Pt 19):3419-31
references.pmid: 11682602
references.citation: Dev Cell. 2008 Dec;15(6):801-12
references.pmid: 19081070
references.citation: Mol Cell Biol. 1994 May;14(5):2985-93
references.pmid: 7513049
references.citation: J Invest Dermatol. 2002 Feb;118(2):216-25
references.pmid: 11841536
references.citation: Development. 2001 Oct;128(19):3843-53
references.pmid: 11585809
references.citation: J Embryol Exp Morphol. 1976 Dec;36(3):597-607
references.pmid: 1010981
references.citation: Genomics. 2002 Nov;80(5):487-98
references.pmid: 12408966
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14677-82
references.pmid: 16203973