Multiple doublesex-Related Genes Specify Critical Cell Fates in a C. elegans Male Neural Circuit 英文参考文献.docVIP

Multipledoublesex-RelatedGenesSpecifyCriticalCell FatesinaC.elegansMaleNeuralCircuit MeaganS.Siehr1.,PamelaK.Koo1.,AmritaL.Sherlekar1.,XuelinBian1,MeredithR.Bunkers1,ReneeM. Miller2,DouglasS.Portman2,RobynLints1* 1DepartmentofBiology,TexasAMUniversity,CollegeStation,Texas,UnitedStatesofAmerica,2DepartmentofBiomedicalGenetics,CenterforNeuralDevelopment andDisease,UniversityofRochester,Rochester,NewYork,UnitedStatesofAmerica Abstract Background:Inmostanimalspecies,malesandfemalesexhibitdifferencesinbehaviorandmorphologythatrelatetotheir respective roles in reproduction. DM (Doublesex/MAB-3) domain transcription factors are phylogenetically conserved regulatorsofsexualdevelopment.Theyarethoughttoestablishsexualtraitsbysex-specificallymodifyingtheactivityof general developmental programs. However, there are few examples where the details of these interactions are known, particularlyinthenervoussystem. Methodology/Principal Findings: In this study, we show that two C. elegans DM domain genes, dmd-3 and mab-23, regulatesensoryandmusclecelldevelopmentinamaleneuralcircuitrequiredformating.Usinggeneticapproaches,we show that in the circuit sensory neurons, dmd-3 and mab-23 establish the correct pattern of dopaminergic (DA) and cholinergic (ACh) fate. We find that the ETS-domain transcription factor gene ast-1, a non-sex-specific, phylogenetically conserved activator of dopamine biosynthesis gene transcription, is broadly expressed in the circuit sensory neuron population.However,dmd-3andmab-23repressitsactivityinmostcells,promotingAChfateinstead.Asubsetofneurons, preferentiallyexposedtoaTGF-betaligand,escapethisrepressionbecausesignaltransductionpathwayactivityinthese cells blocks dmd-3/mab-23 function, allowing DA fate to be established. Through optogenetic and pharmacological approaches,weshowthatthesensoryandmusclecellcharacteristicscontrolledbydmd-3andmab-23arecrucialforcircuit function. Conclusions/Significance:IntheC.elegansmale,DMdomaingenesdmd-3andmab-23regulateexpre