nev (cyfip2) is required for retinal lamination and axon guidance in the zebrafish retinotectal system

摘要

Inthezebrafishretinotectalsystem,retinalganglioncells(RGCs)projecttopographicallyalonganteriorndash;posterior(A-P)anddorsalndash;ventral(D-V)axestoinnervatetheirprimarytarget,theoptictectum.Intheemnevermind/em(emnev/em)mutant,D-Vpositionalinformationisnotmaintainedbydorsonasalretinalaxonsastheyprojectthroughtheoptictracttothetectum.Herewepresentadetailedphenotypicanalysisoftheretinotectalprojectioninemnev/emandshowthatdorsonasalaxonsdoeventuallyfindtheircorrectlocationonthetectum,albeitaftertakingacircuitouspath.Interestingly,emnev/emseemstobespecificallyrequiredforretinalaxonsbutnotforseveralnon-retinalaxontracts.Inaddition,wefindthatemnev/emisrequiredbothcellautonomouslyandcellnonautonomouslyforproperlaminationoftheretina.Weshowthatemnev/emencodesCyfip2(spanclass="underline"Cy/spantoplasmicspanclass="underline"F/spanMRPspanclass="underline"i/spannteractingspanclass="underline"p/spanrotein2)andisthusthefirstknownmutationinavertebrateCyfipfamilymember.Finally,weshowthatCYFIP2actscellautonomouslyintheD-VsortingofdorsonasalRGCaxonsintheoptictract.CYFIP2isahighlyconservedproteinthatlacksknowndomainsorstructuralmotifsbuthasbeenshowntointeractwithRacandthefragile-Xmentalretardationprotein,suggestingintriguinglinkstocytoskeletaldynamicsandRNAregulation./p/div