The Zinc Finger Protein DIE-1 Is Required for Late Events during Epithelial Cell Rearrangement in C. elegans

摘要

Themechanismbywhichepithelialcellsundergodirectedrearrangementiscentraltomorphogenesis,yettheregulationofthesemovementsremainspoorlyunderstood.Wehaveinvestigatedepithelialcellrearrangement(intercalation)inthedorsalhypodermis,orembryonicepidermis,oftheemC.elegans/emembryobyanalyzingtheemdie-1(w34)/emmutant,whichfailstoundergonormalintercalation.Dorsalhypodermalcellsofemdie-1(w34)/emhomozygousembryosinitiatebutfailtocompletetheprocessofintercalation.Multiphotonmicroscopyrevealsthatintercalatingcellsextendmonopolar,basolateralprotrusionsintheirdirectionofmigration;posteriordorsalhypodermalcellsinemdie-1(w34)/emmutantsappeartoextendprotrusionsnormally,butfailtotranslocatetheircellbodiestocompleterearrangement.Despiteabnormalintercalation,thesubsequentmorphogeneticmovementsthatenclosetheembryowithepithelialcellsandtheprocessofdorsalcellfusionstilloccur.However,elongationoftheembryointoawormlikeshapeisdisruptedinemdie-1(w34)/emembryos,suggestingthatintercalationmaybenecessaryforsubsequentelongationoftheembryo.Actinfilamentsarenotproperlyorganizedwithinthedorsalhypodermisofemdie-1(w34)/emembryos,consistentwithintercalation'sbeinganecessaryprerequisiteforelongation.Theemdie-1/emgeneencodesaC2H2zincfingerproteincontainingfourfingers,whichlikelyactsasatranscriptionalregulator.DIE-1ispresentinthenucleiofhypodermal,muscle,gut,andpharyngealcells;itsdistributionsuggeststhatDIE-1actsineachofthesetissuestoregulatemorphogeneticmovements.emdie-1(w34)/emmutantsdisplaymorphogeneticdefectsinthepharynx,gut,andmusclequadrants,inadditiontothedefectsinthedorsalhypodermis,consistentwiththeDIE-1expressionpattern.MosaicanalysisindicatesthatDIE-1isautonomouslyrequiredintheposteriordorsalhypodermisforintercalation.Ouranalysisdocumentsforthefirsttimethedynamicsofprotrusiveactivityduringepithelialcellrearrangement.Moreover,ouranalysisofemdie-1/emshowsthattheeventsofepithelialcellrearrangementareundertranscriptionalcontrol,andthatearlyandlaterphasesofepithelialcellrearrangementaregeneticallydistinguishable./p/div