Differences in Krox20-Dependent Regulation of Hoxa2 and Hoxb2 during Hindbrain Development

Developmental Biology

Miguel Manzanares¹  Heather Marshall¹  Robb Krumlauf¹  Stefan Nonchev¹  Mark K Maconochie¹ 

[1] Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, United Kingdom

关键词: Krox20;    Hoxa2;    Hoxb2;    hindbrain segmentation;    rhombomeres;    transgenic mice;    pattern formation;    vertebrate evolution;    gene regulation;   

DOI  :  10.1006/dbio.2001.0197

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Duringhindbraindevelopment,segmentalregulationoftheparalogousHoxa2andHoxb2genesinrhombomeres(r)3and5involvesKrox20-dependentenhancersthathavebeenconservedduringtheduplicationofthevertebrateHoxclustersfromacommonancestor.ExaminingtheseevolutionarilyrelatedcontrolregionscouldprovideimportantinsightintothedegreetowhichthebasicKrox20-dependentmechanisms,cis-regulatorycomponents,andtheirorganizationhavebeenconserved.TowardthisgoalwehaveperformedadetailedfunctionalanalysisofamouseHoxa2enhancercapableofdirectingreporterexpressioninr3andr5.Thecombinedactivitiesoffiveseparatecis-regions,inadditiontotheconservedKrox20bindingsites,areinvolvedinmediatingenhancerfunction.ACTTT(BoxA)motifadjacenttotheKrox20bindingsitesisimportantforr3/r5activity.TheBoxAmotifissimilartoone(Box1)foundintheHoxb2enhancerandindicatesthatthecloseproximityoftheseBoxmotifstoKrox20sitesisacommonfeatureofKrox20targetsinvivo.Twootherrhombomericelements(RE1andRE3)areessentialforr3/r5activityandsharecommonTCTmotifs,indicatingthattheyinteractwithasimilarcofactor(s).TCTmotifsarealsofoundintheHoxb2enhancer,suggestingthattheymaybeanothercommonfeatureofKrox20-dependentcontrolregions.ThetworemainingHoxa2cis-elements,RE2andRE4,arenotconservedintheHoxb2enhanceranddefinedifferencesinsomeofcomponentsthatcancontributetotheKrox20-dependentactivitiesoftheseenhancers.Furthermore,analysisofregulatoryactivitiesoftheseenhancersinaKrox20mutantbackgroundhasuncovereddifferencesintheirdegreeofdependenceuponKrox20forsegmentalexpression.Together,thisworkhasrevealedasurprisingdegreeofcomplexityinthenumberofcis-elementsandregulatorycomponentsthatcontributetosegmentalexpressionmediatedbyKrox20andshedslightonthediversityandevolutionofKrox20targetsitesandHoxregulatoryelementsinvertebrates.

【 授权许可】

Unknown