Regulation of Rho Family GTPases Is Required to Prevent Axons from Crossing the Midline

[摘要] RhofamilyGTPasesareidealcandidatestoregulateaspectsofcytoskeletaldynamicsdownstreamofaxonguidancereceptors.ToexaminetheinvivoroleofRhoGTPasesinmidlineguidance,dominantnegative(dn)andconstitutivelyactive(ct)formsofRho,Drac1,andDcdc42areexpressedintheDrosophilaCNS.Whenexpressedalone,onlyctDracandctDcdc42causeaxonsinthepCC/MP2pathwaytocrossthemidlineinappropriately.HeterozygouslossofRoundaboutenhancesthectDracphenotypeandcauseserrorsinembryosexpressingdnRhoorctRho.HomozygouslossofSon-of-Sevenless(Sos)alsoenhancesthectDracphenotypeandcauseserrorsinembryosexpressingeitherdnRhoordnDrac.CtRhosuppressesthemidlinecrossingerrorscausedbylossofSos.CtDracandctDcdc42phenotypesaresuppressedbyheterozygouslossofProfilin,butstronglyenhancedbycoexpressionofconstitutivelyactivemyosinlightchainkinase(ctMLCK),whichincreasesmyosinIIactivity.ExpressionofctMLCKalsocauseserrorsinembryosexpressingeitherdnRhoorctRho.OurdataconfirmthatRhofamilyGTPasesarerequiredforregulationofactinpolymerizationand/ormyosinactivityandthatthisiscriticalfortheresponseofgrowthconestomidlinerepulsivesignals.Midlinerepulsionappearstorequiredown-regulationofDrac1andDcdc42andactivationofRho.

[学科分类] 生物科学（综合）

[关键词] Rho;Rac;Cdc42;myosin;actin;Robo;Sos;axon guidance;Drosophila