Gene expression during sex determination reveals a robust female genetic program at the onset of ovarian development

摘要

Theprimaryeventinmammaliansexualdevelopmentisthedifferentiationofthebipotentialgonadsintoeithertestesorovaries.Ourunderstandingofthemolecularpathwaysspecifyinggonadaldifferentiationisstillincomplete.Toidentifytheinitialmolecularchangesaccompanyinggonadaldifferentiationinmice,wehaveperformedalarge-scaletranscriptionalanalysisofXXandXYSf1-positivegonadalcellsduringsexdetermination.Inbothmaleandfemalegenitalridges,arobustgeneticprogramisinitiatedpre-datingthefirstmorphologicalchangesofthedifferentiatinggonads.BetweenE10.5andE13.5,2306geneswereexpressedinasex-specificmannerinthesomaticcompartmentofthegonads;1223wereoverexpressedinXXembryosand1083inXYembryos.Althoughsexuallydimorphicgeneswerescatteredthroughoutthemousegenome,weidentifiedchromosomalregionshostingclustersofgenesdisplayingsimilarexpressionprofiles.Thecyclin-dependentkinaseinhibitorsemCdkn1a/emandemCdkn1c/emareoverexpressedinXXgonadsatE11.5andE12.5,suggestingthattheincreasedproliferationofXYgonadsrelativetoXXgonadsmayresultfromtheoverexpressionofcellcycleinhibitorsinthedevelopingovaries.Thesestudiesdefinethemajorcharacteristicsoftesticularandovariantranscriptionalprogramsandrevealtherichnessofsignalingprocessesindifferentiationofthebipotentialgonadsintotestesandovaries./p/div