Localized BMP4–Noggin Interactions Generate the Dynamic Patterning of Noggin Expression in Somites

摘要

InteractionsbetweenBMP4anditsinhibitor,noggin,regulatepatterningofsomitesandneuralcrest.Duringmesodermdevelopment,nogginmRNAisexpressedintheintermediatemesoderm.Uponsegmentation,itisdetectedinthelateralportionofepithelialsomitesbecomingprogressivelymedializedastheymature.Indissociatedsegments,nogginbecomestransientlyconfinedtothedorsomediallipofthedermomyotome.Here,weinvestigatedthefactor(s)thatcontrolthislateral-to-medialshiftintranscriptionofsomiticnoggin.InhibitionofBMPactivityinthecaudallateralplate/intermediatemesodermpreventednoggintranscriptioninthelateralsomite.Furtherrostrally(orlaterindevelopment),inhibitionoftube-derivedBMP,butnotofWntactivity,preventedinitialnogginexpressioninthedorsomediallipofthedermomyotome.Moreover,BMP4wassufficienttotriggerinitialexpressionofnogginevenintheabsenceofectodermand/orneuraltube,suggestingadirectactiononthedorsomedialsomite.Thus,thepatternsofnoggintranscriptioninsomitesaredirectlyregulatedbyBMP4activitiesemanatingfirstfromthemesodermandlaterfromtheneuraltube.ExpressionpatternsofBMP4andoftypeIABMPreceptorsarespatiotemporallycompatiblewiththislateral-to-medialshift.Theseresultshighlighttheexistenceintheneuraltubea€“mesodermcomplexofaregulatoryloopbywhichBMPpositivelyregulatestranscriptionofnoggin,whichinturnrepressesfurtherligandactivity.