Combinatorial roles for zebrafish retinoic acid receptors in the hindbrain, limbs and pharyngeal arches

摘要

Retinoicacid(RA)signalingregulatesmultipleaspectsofvertebrateembryonicdevelopmentandtissuepatterning,inpartthroughthelocalavailabilityofnuclearhormonereceptorscalledretinoicacidreceptors(RARs)andretinoidreceptors(RXRs).RAR/RXRheterodimerstransducetheRAsignal,andloss-of-functionstudiesinmicehavedemonstratedrequirementsfordistinctreceptorcombinationsatdifferentstagesofembryogenesis.However,thetissue-specificfunctionsofeachreceptorandtheirindividualcontributionstoRAsignalinginvivoareonlypartiallyunderstood.HereweusemorpholinooligonucleotidestodepletethefourknownzebrafishRARs(emraraa/em,emrarab/em,emrarga/em,andemrargb/em).Weshowthatwhileallfourarerequiredforanteriorndash;posteriorpatterningofrhombomeresinthehindbrain,thereareuniquerequirementsforemrarga/eminthecranialmesodermforhindbrainpatterning,andemrarab/eminlateralplatemesodermforspecificationofthepectoralfins.Inaddition,thealphasubclass(emraraa/em,emrarab/em)isRAinducible,andoftheseonlyemraraa/emexpressionisRA-dependent,suggestingthatthesereceptorsestablisharegionofparticularlyhighRAsignalingthroughpositive-feedback.Thesestudiesrevealnoveltissue-specificrolesforRARsincontrollingthecompetenceandsensitivityofcellstorespondtoRA./p/div