Analysis of transcriptional codes for zebrafish dopaminergic neurons reveals essential functions of Arx and Isl1 in prethalamic dopaminergic neuron development

摘要

Distinctgroupsofdopaminergicneuronsdevelopatdefinedanatomicalsitesinthebraintomodulatefunctionofalargediversityoflocalandfar-rangingcircuits.However,themolecularidentityasjudgedfromtranscriptionfactorexpressionhasnotbeendeterminedforalldopaminergicgroups.Here,weanalyzeregionalexpressionoftranscriptionfactorsinthelarvalzebrafishbraintodetermineco-expressionwiththeTyrosinehydroxylasemarkerindopaminergicneurons.Wedefinesetsoftranscriptionfactorsthatclearlyidentifyeachdopaminergicgroup.Thesedataconfirmpostulatedrelationstodopaminergicgroupsdefinedformammaliansystems.Wefocusourfunctionalanalysisonprethalamicdopaminergicneurons,whichco-expressthetranscriptionfactorsArxandIsl1.Morpholino-basedknockdownrevealsthatbothArxandIsl1arestrictlyrequiredforprethalamicdopaminergicneurondevelopmentandappeartoactinparallel.WefurthershowthatArxcontributestopatterningintheprethalamicregion,whileIsl1isrequiredfordifferentiationofprethalamicdopaminergicneurons./p/div