REGULATION OF DORSAL SOMITIC CELL FATES - BMPS AND NOGGIN CONTROL THETIMING AND PATTERN OF MYOGENIC REGULATOR EXPRESSION

Previous work has indicated that signals from the neural tube, notocho rd, and surface ectoderm promote somitic myogenesis. Here, we show tha t somitic myogenesis is under negative regulation as well; BMP signali ng serves to inhibit the activation of MyoD and Myf5 in Pax3-expressin g cells. Furthermore, we show that the BMP antagonist Noggin is expres sed within the dorsomedial lip of the dermomyotome, where Pax3-express ing cells first initiate the expression of MyoD and Myf5 to give rise to myotomal cells in the medial somite. Consistent with the expression of Noggin in dorsomedial dermomyotomal cells that lie adjacent to the dorsal neural tube, we have found that coculture of somites with fibr oblasts programmed to secrete Wnt1, which is expressed in dorsal neura l tube, call induce semitic Noggin expression. Ectopic expression of N oggin lateral to the somite dramatically expands MtoD expression into the lateral regions of the somite, represses Pax3 expression in this t issue, and induces formation of a lateral myotome. Together, our findi ngs indicate that the timing and location of myogenesis within the som ite is controlled by relative levels of BMP activity and localized exp ression of a BMP antagonist.