Extracellular matrix-modulated Heartless signaling in Drosophila blood progenitors regulates their differentiation via a Ras/ETS/FOG pathway and target of rapamycin function

摘要

Maintenanceofhematopoieticprogenitorsensuresacontinuoussupplyofbloodcellsduringthelifespanofanorganism.Thus,understandingthemolecularbasisforprogenitormaintenanceisacontinuedfocusofinvestigation.AlargepoolofundifferentiatedbloodprogenitorsaremaintainedintheemDrosophila/emhematopoieticorgan,thelarvallymphgland,byacomplexnetworkofsignalingpathwaysthataremediatedbyniche-,progenitor-,ordifferentiatedhemocyte-derivedsignals.InthisstudyweexaminedthefunctionoftheemDrosophila/emfibroblastgrowthfactorreceptor(FGFR),Heartless,acriticalregulatorofearlylymphglandprogenitorspecificationinthelateembryo,duringlarvallymphglandhematopoiesis.ActivationofHeartlesssignalinginhemocyteprogenitorsbyitstwoligands,PyramusandThisbe,isbothrequiredandsufficienttoinduceprogenitordifferentiationandformationoftheplasmatocyte-richlymphglandcorticalzone.WeidentifytwotranscriptionalregulatorsthatfunctiondownstreamofHeartlesssignalinginlymphglandprogenitors,theETSprotein,Pointed,andtheFriend-of-GATA(FOG)protein,U-shaped,whicharerequiredforthisHeartless-induceddifferentiationresponse.Furthermore,cross-talkofHeartlessandtargetofrapamycinsignalinginhemocyteprogenitorsisrequiredforlamellocytedifferentiationdownstreamofThisbe-mediatedHeartlessactivation.Finally,weidentifytheemDrosophila/emheparansulfateproteoglycan,Trol,asacriticalnegativeregulatorofHeartlessligandsignalinginthelymphgland,demonstratingthatsequestrationofdifferentiationsignalsbytheextracellularmatrixisauniquemechanismemployedinbloodprogenitormaintenancethatisofpotentialrelevancetomanyotherstemcellniches./p/div