The Mouse Kreisler (Krml1/MafB) Segmentation Gene Is Required for Differentiation of Glomerular Visceral Epithelial Cells

Developmental Biology

Joanna Yu¹  Susan E. Quaggin¹  Greg S. Barsh¹  Douglas Holmyard¹  Fuzi Jin¹  Virginia S. Sadl¹  Sabine P. Cordes¹  Shiying Cui¹ 

[1] Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, University of Toronto, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada

关键词: Kreisler (Krml1/MafB);    Pod1 (epicardin/capsulin);    podocyte;    kidney disease;    cellular differentiation;    proteinuria;   

DOI  :  10.1006/dbio.2002.0751

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Molecularcomponentsoftheglomerularfiltrationmechanismplaycriticalrolesinrenaldiseases.Manyofthesecomponentsareproducedduringthefinalstagesofdifferentiationofglomerularvisceralepithelialcells,alsoknownaspodocytes.Whilebasicdomainleucinezipper(bZip)transcriptionfactorsoftheMafsubfamilyhavebeenimplicatedincellulardifferentiationprocesses,Kreisler(Krml1/MafB),thegeneaffectedinthemousekreisler(kr)mutation,isknownforitsroleinhindbrainpatterning.HereweshowthatmicehomozygousforthekrenumutationdeveloprenaldiseaseandthatKreislerisessentialforcellulardifferentiationofpodocytes.Consistentwithabnormalpodocytedifferentiation,krenuhomozygotesshowproteinuria,andfusionandeffacementofpodocytefootprocesses,whicharealsoobservedinthenephroticsyndrome.Kreisleractsduringthefinalstagesofglomerulardevelopment—thetransitionbetweenthecapillaryloopandmaturestages—anddownstreamofthePod1basicdomainhelix–loop–helixtranscriptionfactor.ThelevelsofPodocin,thegenemutatedinautosomalrecessivesteroid-resistantnephroticsyndrome(NPHS2),andNephrin,thegenemutatedincongenitalnephroticsyndromeoftheFinnishtype(NPHS1),areslightlyreducedinkrenu/krenupodocytes.However,theseobservationsaloneareunlikelytoaccountfortheaberrantpodocytefootprocessformation.Thus,Kreislermustregulateotherunknowngenesrequiredforpodocytefunctionandwithpossiblerolesinkidneydisease.

【 授权许可】

Unknown