Characterization and regulation of the hb9/mnx1 beta-cell progenitor specific enhancer in zebrafish

Developmental Biology

Dirk Meyer¹  Valeriya Arkhipova¹  Björn Wendik³  Olivier Ek²  Nathalie Devos²  Bernard Peers² 

[1] Institute for Molecular Biology/CMBI, Technikerstr. 25, University of Innsbruck, 6020 Innsbruck, Austria;Laboratory of Molecular Biology and Genetic Engineering, University Liège, Avenue de l'hopital 1, GIGA-R, Bâtiment B34, Liège, Sart Tilman, B-4000, Belgium;Developmental Biology, Institute Biology 1, University of Freiburg, Hauptstrasse 1, 79104 Freiburg, Germany

DOI  :  10.1016/j.ydbio.2012.03.001

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Differentiationofinsulinproducingbeta-cellsisageneticallywelldefinedprocessthatinvolvesfunctionsofvariousconservedtranscriptionfactors.Still,thetranscriptionalmechanismsunderlyingspecificationanddeterminationofbeta-cellfatearepoorlydefined.Hereweprovidethedescriptionofabeta-cellprogenitorspecificenhancerasamodeltostudyinitialstepsofbeta-celldifferentiation.Weshowthatevolutionarynon-conservedupstreamsequencesofthezebrafishhb9genearerequiredandsufficientforregulatingexpressioninbeta-cellspriortotheonsetofinsulinexpression.Thisenhancercontainsbindingsitesforpaired-boxtranscriptionfactorsandtwoE-boxesthatinEMSAstudiesshowinteractionwithPax6bandNeuroD,respectively.WeshowthatPax6bisapotentactivatorofendodermalhb9expressionandthatthisactivationdependsonthebeta-cellenhancer.Usinggeneticapproachesweshowthatpax6biscrucialformaintenancebutnotinductionofpancreatichb9transcription.AslossofPax6borHb9independentlyresultsinthelossofinsulinexpression,thedatarevealanovelcross-talkbetweenthetwoessentialregulatorsofearlybeta-celldifferentiation.WhilewefindthattheknownpancreaticE-boxbindingproteinsNeuroDandNgn3arenotrequiredforhb9expressionwealsoshowthatremovalofbothE-boxesselectivelyeliminatespancreaticspecificreporterexpression.ThedataprovideevidenceforanNgn3independentpathwayofbeta-cellspecificationthatrequiresfunctionofcurrentlynotspecifiedE-boxbindingfactors.

【 授权许可】

Unknown   

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