Cyclic Expression of Lhx2 Regulates Hair Formation 英文参考文献.docVIP

CyclicExpressionofLhx2RegulatesHairFormation GunillaTo¨rnqvist.,AnnaSandberg.,Anna-CarinHa¨gglund,LeifCarlsson* Umea? CenterforMolecularMedicine,Umea? University,Umea?, Sweden Abstract Hairisimportantforthermoregulation,physicalprotection,sensoryactivity,seasonalcamouflage,andsocialinteractions. Hairisgeneratedinhairfollicles(HFs)and,followingmorphogenesis,HFsundergocyclicphasesofactivegrowth(anagen), regression (catagen), and inactivity (telogen) throughout life. The transcriptional regulation of this process is not well understood.WeshowthatthetranscriptionfactorLhx2isexpressedincellsoftheouterrootsheathandasubpopulationof matrix cells during both morphogenesis and anagen. As the HFs enter telogen, expression becomes undetectable and reappearspriortoinitiationofanageninthesecondaryhairgerm.Incontrasttopreviouslypublishedresults,wefindthat Lhx2 is primarily expressed by precursor cells outside of the bulge region where the HF stem cells are located. This developmental,stage-andcell-specificexpressionsuggeststhatLhx2regulatesthegenerationandregenerationofhair.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, primarilyinprecursorcellsdistinctfromthoseinthebulgeregion,andisanessentialpositiveregulatorofhairformation. Citation:To¨rnqvistG,SandbergA,Ha¨gglundA-C,CarlssonL(2010)CyclicExpressionofLhx2RegulatesHairFormation.PLoSGenet6(4):e1000904.doi:10.1371/ journal.pgen.1000904 Editor:GregoryS.Barsh,StanfordUniversitySchoolofMedicine,UnitedStatesofAmerica ReceivedOctober26,2009;AcceptedMarch9,2010;PublishedApril8,2010 Copyright: ? 2010 To¨rnqvist et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits