SONIC HEDGEHOG IS REQUIRED FOR SURVIVAL OF BOTH MYOGENIC AND CHONDROGENIC SOMITIC LINEAGES

In vertebrates, the medial moieties of the somites give rise to the ve rtebrae and epaxial muscles, which develop in close relationship with the axial organs, neural tube and notochord, The lateral moieties cont ribute to the ribs and to Limb and body wall muscles (hypaxial muscles ) after a phase of lateral and ventral migration. Surgical ablation of the neural tube and notochord in the chick embryo during segmentation and early differentiation of the somites (day 2 of incubation) does n ot affect primary development of the hypaxial muscles, but leads to a complete absence of epaxial muscles, vertebrae and ribs, due to cell d eath in the somites, Here we demonstrate that cell death, which occurs within 24 hours of excision of the axial organs, affects both myogeni c and chondrogenic cell lineages defined, respectively, by the express ion of MyoD and Pax-1 genes. In contrast, Pax-3 transcripts, normally present in cells giving rise to hypaxial muscles, are preserved in the excised embryos. Backgrafting either the ventral neural tube or the n otochord allows survival of MyoD- and Pax-1-expressing cells. Similarl y, Sonic hedgehog-producing cells grafted in place of axial organs als o rescue MyoD- and Pax-1-expressing cells from death and allow epaxial muscles, ribs and vertebrae to undergo organogenesis, These results d emonstrate that the ventral neural tube and the notochord promote the survival of both myogenic and chondrogenic cell lineages in the somite s and that this action is mediated by Sonic hedgehog.