Dominant Drop Mutants Are Gain-of-Function Alleles of the muscle segment homeobox Gene (msh) Whose Overexpression Leads to the Arrest of Eye Development

Developmental Biology

Brian A Mozer¹ 

[1] Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892

关键词: Drosophila;    msh;    Drop;    eye development;    gain-of-function mutation;    morphogenetic furrow;   

DOI  :  10.1006/dbio.2001.0229

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

DominantDrop(Dr)mutationsarenearlyeyelessandhaveadditionalrecessivephenotypesincludinglethalityandpatterningdefectsineyeandsensorybristlesduetocis-regulatorylesionsinthecellcycleregulatorstring(stg).Geneticanalysisdemonstratesthatthedominantsmalleyephenotypeistheresultofseparategain-of-functionmutationsinthecloselylinkedmusclesegmenthomeobox(msh)gene,encodingahomeodomaintranscriptionfactorrequiredforpatterningofmuscleandnervoussystem.ReversionoftheDrMioallelewascoincidentwiththegenerationoflethalloss-of-functionmutationsinmshincis,suggestingthatthedominanteyephenotypeistheresultofectopicexpression.MoleculargeneticanalysisrevealedthattwodominantDrallelescontainlesionsupstreamofthemshtranscriptionstartsite.IntheDrMiomutant,a3S18retrotransposoninsertionisthetargetofsecond-sitemutations(P-elementinsertionsordeletions)whichsuppressthedominanteyephenotypefollowingreversion.Thepatternof3S18expressionandtheabsenceofmshineyeimaginaldiscssuggestthattranscriptionalactivationofthemshpromoteraccountsforectopicexpression.Drdominantmutationsarresteyedevelopmentbyblockingtheprogressionofthemorphogeneticfurrowleadingtophotoreceptorcelllossviaapoptosis.Gal4-mediatedubiquitousexpressionofmshinthird-instarlarvaewassufficienttoarrestthemorphogeneticfurrowintheeyeimaginaldiscandresultedinlethalitypriortoeclosion.Dominantmutationsinthehumanmsx2gene,oneofthevertebratehomologsofmsh,areassociatedwithcraniosynostosis,adiseaseaffectingcranialdevelopment.TheDrmutationsarethefirstexampleofgain-of-functionmutationsinthemsh/msxgenefamilyidentifiedinageneticallytractiblemodelorganismandmayserveasausefultooltoidentifyadditionalgenesthatregulatethisclassofhomeodomainproteins.

【 授权许可】

Unknown