Novel gain-of-function alleles demonstrate a role for the heterochronic gene lin-41 in C. elegans male tail tip morphogenesis

摘要

Togainanunderstandingofthegenesandmechanismsthatgovernmorphogenesisanditsevolution,wehaveanalyzedmutationsthatdisruptthisprocessinasimplemodelstructure,themaletailtipoftherhabditidnematodeemC.elegans/em.Duringtheevolutionofrhabditidmaletails,therehavebeenseveralindependentchangesfromtailswithroundedtips(ldquo;peloderanrdquo;,asinemC.elegans/em)tothosewithpointedtips(ldquo;leptoderanrdquo;).Mutationswhichproduceleptoderan(Lep)tailsinemC.elegans/emthusidentifycandidategenesandpathwaysinwhichevolutionarychangescouldhaveproducedleptoderantailsfrompeloderanancestors.Herewereportthattwonovel,gain-of-function(gf)allelesofemlin-41/emhavelesionspredictedtoaffecttheN-terminusoftheRBCC-domainLIN-41protein.Bothgfallelescausethetailtipofadultmalestoretainthepointedshapeofthejuveniletails,producingaLepphenotypethatlookslikethetailsofleptoderanspecies.Consistentwithitsroleintheheterochronicpathway,wefindthatemlin-41/emgovernsthetimingandextentofmaletailtipmorphogenesisinadose-dependentmanner.Specifically,theLepphenotyperesultsfromaheterochronicdelayintheretractionandfusionofthetailtipcellsduringL4morphogenesis,suchthatretractionisnotcompletedbeforetheadultmolt.Conversely,wefindthattailtipmorphogenesisandcellfusionsbeginprecociouslyattheL3stageinthereduced-functionemlin-41/emmutant,emma104/em,resultinginover-retractedmaletailsintheadult.Becausemodulatedanti-LIN-41RNAiknockdownsinthegfmutantsrestorewild-typephenotype,wesuggestthattheleptoderanphenotypeofthegfallelesisduetoahigheractivityofotherwisenormalLIN-41.Additionally,thegfalleleissuppressedbythewild-typeallele,suggestingthatLIN-41normallyregulatesitself,possiblybyautoubiquitination.WespeculatethatsmallchangesaffectingLIN-41couldhavebeensignificantformaletailevolution./p/div