A gradient of Shh establishes mutually repressing somitic cell fates induced by Nkx3.2 and Pax3

摘要

WntandSonicHedgehog(Shh)signalsareknowntopatternthesomiteintodermomyotomal,myotomalandsclerotomalcellfates.ByemployingexplantsofpresomiticmesodermculturedwithconstantlevelsofWnt3aconditionedmediumandincreasinglevelsofShh,wefoundthatdifferinglevelsofShhsignalingelicitdifferingresponsesfromsomiticcells:thelowestlevelofShhsignalingallowsdermomyotomalgeneexpression,intermediatelevelsinducelossofdermomyotomalmarkersandactivationofmyogenicdifferentiation,andhigherlevelsinducelossofmyotomalmarkersandactivationofsclerotomalgeneexpression.Inaddition,wehavefoundthatinthepresenceofhighlevelsofWntsignaling,insteadofinducingsclerotomalmarkers,Shhsignalsacttomaintaintheexpressionofdermomyotomalandmyotomalmarkers.OneofthesclerotomalgenesinducedbyhighlevelsofShhsignalingisNkx3.2.ForcedexpressionofNkx3.2blockssomiticexpressionofthedermomyotomalmarkerPax3bothinvitroandinvivo.Conversely,forcedexpressionofPax3insomitescanblockShh-mediatedinductionofsclerotomalgeneexpressionandchondrocytedifferentiationinvitro.ThusweproposethatvaryinglevelsofShhsignalingactinamorphogen-likemannertoelicitdifferingresponsesfromsomiticcells,andthatPax3andNkx3.2setupmutuallyrepressingcellfatesthatpromoteeitherdermomyotome/myotomeorsclerotomedifferentiation,respectively./p/div