A conserved mechanism for vertebrate mesoderm specification in urodele amphibians and mammals

摘要

Understandinghowmesodermisspecifiedduringdevelopmentisafundamentalissueinbiology,andithasbeenstudiedintensivelyinembryosfromemXenopus/em.Thegeneregulatorynetwork(GRN)foremXenopus/emissurprisinglycomplexandisnotconservedinvertebrates,includingmammals,whichhavesinglecopiesofthekeygenesNodalandMix.WhytheemXenopus/emGRNshouldexpressmultiplecopiesofNodalandMixgenesisnotknown.Tounderstandhowtheseexpandedgenefamiliesevolved,weinvestigatedmesodermspecificationinembryosfromaxolotls,representingurodeleamphibians,sinceurodeleembryologyisbasaltoamphibiansandwasconservedduringtheevolutionofamniotes,includingmammals.WeshowthatsinglecopiesofNodalandMixarerequiredformesodermspecificationinaxolotlembryos,suggestingtheancestralvertebratestate.Furthermore,weuncoveredanovelgeneticinteractioninwhichMixinducesBrachyuryexpression,standingincontrasttotherelationshipofthesemoleculesinemXenopus/em.However,wedemonstratethatthisfunctionalrelationshipisconservedinmammalsbyshowingthatitisinvolvedintheproductionofmesodermfrommouseembryonicstemcells.Fromourresults,weproducedanancestralmesoderm(m)GRN,whichwesuggestisconservedinvertebrates.Theresultsarediscussedwithinthecontextofatheoryinwhichtheevolutionofmechanismsgoverningearlysomaticdevelopmentisconstrainedbytheancestralgermlinendash;somarelationship,inwhichgermcellsareproducedbyepigenesis./p/div