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

Developmental Biology

Janice L. Fritz¹  Mark F.A. VanBerkum¹ 

[1] Department of Biological Sciences, Wayne State University, Detroit, Michigan, 48202

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

DOI  :  10.1006/dbio.2002.0842

学科分类：生物科学（综合）

来源: Academic Press

【 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.

【 授权许可】

Unknown