Robo–Slit interactions regulate longitudinal axon pathfinding in the embryonic vertebrate brain

摘要

Theearlynetworkofaxonsintheembryonicbrainprovidesconnectivitybetweenfunctionallydistinctregionsofthenervoussystem.Whilemanyofthemolecularinteractionsdrivingcommissuralpathwayformationhavebeendeciphered,themechanismsunderlyingthedevelopmentoflongitudinaltractsremainunclear.WehaveidentifiedherearolefortheRoundabout(Robo)familyofaxonguidancereceptorsinthepositioningoflongitudinallyprojectingaxonsalongthedorsoventralaxisintheembryoniczebrafishforebrain.Usingaloss-of-functionapproach,weestablishedthatRobofamilymembersexhibitcomplementaryfunctionsinthetractofthepostopticcommissure(TPOC),themajorlongitudinaltractintheforebrain.Robo2actedinitiallytosplittheTPOCintodiscretefasciclesuponenteringabroaddomainofSlit1aexpressionintheventrocaudaldiencephalon.Incontrast,Robo1andRobo3restrictedtheextentofdefasciculationoftheTPOC.Inthisway,thecomplementaryrolesofRobofamilymembersbalancelevelsoffasciculationanddefasciculationalongthistrajectory.TheseresultsdemonstrateakeyroleforRobondash;Slitsignalinginvertebratelongitudinalaxonguidanceandhighlighttheimportanceofcontext-specificguidancecuesduringnavigationwithincomplexpathways./p/div