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