A dynamic gradient of Wnt signaling controls initiation of neurogenesis in the mammalian cortex and cellular specification in the hippocampus

摘要

Neurogenesisinthedevelopingneocortexisastrictlyregulatedprocessofcelldivisionanddifferentiation.HerewereportthatagradualretreatofcanonicalWntsignalinginthecortexfromlateral-to-medialandanterior-to-posteriorisaprerequisiteofneurogenesis.Ectopicexpressionofaβ-catenin/LEF1fusionproteinmaintainsactivecanonicalWntsignalinginthedevelopingcortexanddelaystheexpressiononsetoftheneurogenicfactorsPax6,Ngn2andTbr2andsubsequentneurogenesis.Contrarytothis,conditionalablationofβ-cateninacceleratesexpressionofthesameneurogenicgenes.Furthermore,weshowthatasustainedcanonicalWntactivityinthelateralcortexgivesrisetocellswithhippocampalcharacteristicsinthecorticalplateattheexpenseofthecorticalfate,andtocellswithdentategyruscharacteristicsinthehippocampus.ThissuggeststhatthedoseofcanonicalWntsignalingdeterminescellularfateinthedevelopingcortexandhippocampus,andthatrecessionofWntsignalingactsasamorphogeneticgradientregulatingneurogenesisinthecortex./p/div