Conservation and Diversity in the cis-Regulatory Networks That Integrate Information Controlling Expression of Hoxa2 in Hindbrain and Cranial Neural Crest Cells in Vertebrates

Developmental Biology

Mark Maconochie¹  Stefan Tümpel¹  Robb Krumlauf¹  Leanne M. Wiedemann¹ 

[1] Stowers Institute, 1000 East 50th, Kansas City, Missouri, 64110

关键词: Hoxa2;    Hoxb2;    hindbrain;    neural crest cells;    segmentation;    regulation;    conservation;    gene expression;    vertebrates;    evolution;   

DOI  :  10.1006/dbio.2002.0665

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

TheHoxa2andHoxb2genesaremembersofparalogygroupIIanddisplaysegmentalpatternsofexpressioninthedevelopingvertebratehindbrainandcranialneuralcrestcells.Functionalanalyseshavedemonstratedthatthesegenesplaycriticalrolesinregulatingmorphogeneticpathwaysthatdirecttheregionalidentityandanteroposteriorcharacterofhindbrainrhombomeresandneuralcrest-derivedstructures.Transgenicregulatorystudieshavealsobeguntocharacterizeenhancersandcis-elementsforthosemouseandchickengenesthatdirectrestrictedpatternsofexpressioninthehindbrainandneuralcrest.InlightoftheconservedroleofHoxa2inneuralcrestpatterninginvertebratesandthesimilaritiesbetweenparalogs,itisimportanttounderstandtheextenttowhichcommonregulatorynetworksandelementshavebeenpreservedbetweenspeciesandbetweenparalogs.Toinvestigatethisproblem,wehaveclonedandsequencedtheintergenicregionbetweenHoxa2andHoxa3inthechickHoxAcomplexanduseditformakingcomparativeanalyseswiththerespectivehuman,mouse,andhornsharkregions.WehavealsousedtransgenicassaysinmouseandchickembryostotestthefunctionalactivityofHoxa2enhancersinheterologousspecies.OuranalysisrevealsthatthreeofthecriticalindividualcomponentsoftheHoxa2enhancerregionfrommousenecessaryforhindbrainexpression(Krox20,BoxA,andTCTmotifs)havebeenpartiallyconserved.However,theirnumberandorganizationarehighlyvariedforthesamegeneindifferentspeciesandbetweenparalogswithinaspecies.Otheressentialmouseelementsappeartohavedivergedorareabsentinchickandshark.Wefindthemouser3/r5enhancerfailstoworkinchickembryosandthechickenhancerworkspoorlyinmice.Thisimpliesthatnewmotifshavebeenrecruitedorutilizedtomediaterestrictedactivityoftheenhancerinotherspecies.Withrespecttoneuralcrestregulation,cis-componentsareembeddedamongthehindbraincontrolelementsandarehighlydivergedbetweenspecies.Hence,therehasbeennowidespreadconservationofsequenceidentityovertheentireenhancerdomainfromsharktohumans,despitethecommonfunctionofthesegenesinheadpatterning.Thisprovidesinsightintohowapparentlyequivalentregulatoryregionsfromthesamegeneindifferentspecieshaveevolveddifferentcomponentstopotentiatetheiractivityincombinationwithaselectionofcorecomponents.

【 授权许可】

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