Experimental Studies on the Spatiotemporal Expression of WT1 and RALDH2 in the Embryonic Avian Heart: A Model for the Regulation of Myocardial and Valvuloseptal Development by Epicardially Derived Cells (EPDCs)

Developmental Biology

A. Wessels¹  J.M. Pérez-Pomares¹  M. Sedmerova¹  R. Carmona¹  M. González-Iriarte¹  R. Muñoz-Chápuli¹  A. Phelps¹ 

[1] Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, Charleston, South Carolina, 29425

关键词: cardiac development;    EPDCs;    epicardium;    RALDH2;    WT1;   

DOI  :  10.1006/dbio.2002.0706

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Epicardiallyderivedcells(EPDCs)delaminatefromtheprimitiveepicardiumthroughanepithelial-to-mesenchymaltransformation(EMT).Afterthistransformation,asubpopulationofcellsprogressivelyinvadesmyocardialandvalvuloseptaltissues.Thefirstaimofthestudywastodeterminethetissue-specificdistributionoftwomoleculesthatarethoughttoplayacrucialfunctionintheinteractionbetweenEPDCsandothercardiactissues,namelytheWilms'Tumortranscriptionfactor(WT1)andretinaldehyde-dehydrogenase2(RALDH2).Thisstudywasperformedinnormalavianandinquail-to-chickchimericembryos.ItwasfoundthatEPDCsthatmaintaintheexpressionofWT1andRALDH2initiallypopulatethesubepicardialspaceandsubsequentlyinvadetheventricularmyocardium.AsEPDCsdifferentiateintothesmoothmuscleandendothelialcelllineageofthecoronaryvessels,theexpressionofWT1andRALDH2becomesdownregulated.Thisprocessisaccompaniedbytheupregulationoflineage-specificmarkers.WealsoobservedEPDCsthatcontinuedtoexpressWT1(butverylittleRALDH2)whichdidnotcontributetotheformationofthecoronarysystem.Asubsetofthesecellseventuallymigratesintotheatrioventricular(AV)cushions,atwhichpointtheynolongerexpressWT1.TheWT1/RALDH2-negativeEPDCsintheAVcushionsdo,however,expressthesmoothmusclecellmarkercaldesmon.Thesecondaimofthisstudywastodeterminetheimpactofabnormalepicardialgrowthoncardiacdevelopment.Experimentaldelayofepicardialgrowthdistortednormalepicardialdevelopment,reducedthenumberofinvasiveWT1/RALDH2-positiveEPDCs,andprovokedanomaliesinthecoronaryvessels,theventricularmyocardium,andtheAVcushions.Wesuggestthattheproperdevelopmentofventricularmyocardiumisdependentontheinvasionofundifferentiated,WT1-positive,retinoicacid-synthesizingEPDCs.Furthermore,weproposethataninteractionbetweenEPDCsandendocardial(derived)cellsisimperativeforcorrectdevelopmentoftheAVcushions.

【 授权许可】

Unknown