The transcription factors AP-2β and AP-2α are required for survival of sympathetic progenitors and differentiated sympathetic neurons

摘要

Differentiationofsympatheticneuronsiscontrolledbyagroupoftranscriptionfactors,includingPhox2b,Ascl1,Hand2andGata3,inducedbybonemorphogeneticproteins(BMPs)inprogenitorslocatedinganglionprimordiaatthedorsalaorta.Here,weaddressthefunctionofthetranscriptionfactorsAP-2βandAP-2α,expressedinmigratingneuralcrestcells(NCC)andmaintainedinsympatheticprogenitorsanddifferentiatedneurons.TheeliminationofbothemAP-2α/emandemAP-2β/emresultsinthevirtuallycompleteabsenceofsympatheticandsensorygangliaduetoapoptoticcelldeathofmigratingNCC.IntheemAP-2β/emknockoutonlysympatheticganglia(SG)aretargeted,leadingtoareductioninganglionsizebyabout40%,whichisalsocausedbyapoptoticdeathofneuralcrestprogenitors.TheconditionaldoubleknockoutofemAP-2α/emandemAP-2β/eminsympatheticprogenitorsanddifferentiatednoradrenergicneuronsresultsinafurtherdecreaseinneuronnumber,leadingeventuallytosmallsympatheticganglionrudimentspostnatally.TheeliminationofemAP-2β/emalsoleadstothecompleteabsenceofnoradrenergicneuronsoftheemLocuscoeruleus/em(LC).WhereasAP-2emα//emβtranscriptionfactorsareinvivonotrequiredfortheonsetormaintenanceofnoradrenergicdifferentiation,theiressentialsurvivalfunctionsaredemonstratedforsympatheticprogenitorsandnoradrenergicneurons./p/div