A defect of the splanchnic mesoderm caused by the mutant gene dominant hemimelia in the mouse☆

[摘要] Themutantgenedominanthemimelia(Dh)causespreaxialabnormalitiesofthehindlimb,reducednumberofpresacralvertebraeandribs,absenceofthespleen,andwidespreadabnormalitiesofthedigestiveandurogenitalsystems.Thedefects,whicharemoresevereinhomozygotes(DhDh)thaninheterozygotes(Dh+),aretraceabletodefectivesplanchnicmesoderminearly912-dayembryos.Atthisstageinnormal(+/+)micethesplanchnicmesoderm,exceptforashortdistanceattheanteriorendoftheintestine,hasanepithelialtypeoforganizationwhichpersistsforvaryingperiodsindifferentareas.Theepitheliumisespeciallythickfromtheanteriorendasfarbackastheprimordiumofthedorsalpancreas.Thisparthasbeencalledtheanteriorsplanchnicmesodermalplate(ASMP).TheepithelialstructureoftheASMPandtheposteriorpartofthesplanchnicmesodermisdiminishedorabsentinDh+andDhDhmice,exceptinthepartfromthelungprimordiaforward.AttheposteriorendofthecoelominDh+andDhDhembryosthemesodermalcells,astheyincreaseinnumber,donotmaintainanepithelialorganization,butaccumulateasunorganizedmesenchyme.Bythetimesegmentationreachestheendofthecoelom,thecoelomisseentobeaboutonesegmentshorterthannormalinDh+andtwosegmentsshorterinDhDh.Theumbilicalarterieswhichformpartoftheposteriorborderofthecoelomarealsodisplacedanteriorly.Itispostulatedthatin+/+embryosatthisstageelongationoftheposteriorendofthecoelomtakesplace,atleastinpart,byanactiveexpansionofthesurfaceepithelium.Intheabsenceofnormalepithelialstructure,thesurfacedoesnotactivelyexpandandthecoelomdoesnotelongatenormally.ThegreateromentumandtheomentalbursaaresmallerthannormalinDh+andDhDh.Themechanismmaybethesameasinthefailureofelongationofthecoelom,i.e.,failureofexpansionofthesurfaceoftheomentalmesenteryasaresultofdefectiveepitheliumoftheASMP.Splanchnicmesodermprobablyinteractswiththeendodermoftheguttopromotethegrowthofthelatter.Thesmallstomachandintestinemayresultfromdefectiveinfluenceofthemesoderm.Thevitellineveinnormallyformsananastomosisthroughthemesodermoverthedorsalsideoftheduodenuminlate912-dayembryos.TheanastomosisfailstoforminDh+andDhDh,presumablybecauseofthedefectivemesoderm.Byaseriesoflaterchangesthisresultsinadisplacedduodenumandformationoftheposteriorvenacavafromtheleftposteriorcardinalveinratherthanfromtheright.In+/+micetheASMPpersistslongestintheregionwherethespleenforms.IntheabsenceoftheASMPinthisregioninDh+andDhDh,thespleendoesnotform.TheshortcoelominDh+andDhDhisabnormallyshapedatitsposteriorend.Thebladder,ureters,urethra,andvagina,whichdevelopinthemesodermhere,areusuallyabnormalinDhDhandoccasionallysoinDh+,presumablyasaresultofabnormalspatialrelationships.Thehindlimbbudbearsaconstantspatialrelationtotheumbilicalartery,andisthereforemoreanteriorinDh+andDhDhthanin+/+.Itissuggestedthattheumbilicalarteryisthelimbbudinductor.Thedisplacedlimbbudresultsinadisplacedpelvicgirdleandthusinfewerpresacralvertebraethannormal.Thereasonforthereducednumberofribsisnotclear.Theabnormalconditionsattheposteriorendofthecoelomareprobablythecauseoftheabnormaldevelopmentofthehindlimbbudleadingtopreaxialdefectsofthelimb.Themechanismofthiseffectisunknown.

[学科分类] 生物科学（综合）