Cross regulation of intercellular gap junction communication and paracrine signaling pathways during organogenesis in Drosophila

摘要

Thespatialandtemporalcoordinationofpatterningandmorphogenesisisoftenachievedbyparacrinemorphogensignalsorbythedirectcouplingofcellsviagapjunctions.Howparacrinesignalsandgapjunctioncommunicationcooperatetocontrolthecoordinatedbehaviorofcellsandtissuesismostlyunknown.Wefoundthathedgehogsignalingisrequiredfortheexpressionofemwingless/emandofemDelta/Notch/emtargetgenesinasinglerowofboundarycellsintheforegut-associatedproventriculusorganoftheemDrosophila/emembryo.Thesecellscoordinatethemovementandfoldingofproventricularcellstogenerateamultilayeredorgan.hedgehogandwinglessregulategapjunctioncommunicationbytranscriptionallyactivatingtheeminnexin2/emgene,whichencodesamemberoftheinnexinfamilyofgapjunctionproteins.Ineminnexin2/emmutants,gapjunction-mediatedcell-to-cellcommunicationisstronglyreducedandtheproventricularcelllayersfailtofoldandinvaginate,similarlyasinemhedgehog/emoremwingless/emmutants.Wefurtherfoundthateminnexin2/emisrequiredinafeedbackloopforthetranscriptionalactivationofthehedgehogandwinglessmorphogensandofDeltaintheproventriculusprimordium.Weproposethatthetranscriptionalcrossregulationofparacrineandgapjunction-mediatedsignalingisessentialfororganogenesisinemDrosophila/em./p/div