CONTROL OF SOMITE PATTERNING BY SONIC HEDGEHOG AND ITS DOWNSTREAM SIGNAL RESPONSE GENES

In the avian embryo, previous work has demonstrated that the notochord provides inductive signals to activate myoD and pax1 regulatory genes , which are expressed in the dorsal and ventral somite cells that give rise to myotomal and sclerotomal lineages, Here, we present bead impl antation and antisense inhibition experiments that show that Sonic hed gehog is both a sufficient and essential notochord signal molecule for myoD and pax1 activation in somites, Furthermore, we show that genes of the Sonic hedgehog signal response pathway, specifically patched, t he Sonic hedgehog receptor, and gli and gli2/4, zinc-finger transcript ion factors, are activated in coordination with somite formation, esta blishing that Sonic hedgehog response genes play a regulatory role in coordinating the response of somites to the constitutive notochord Son ic hedgehog signal, Furthermore, the expression of patched, gli and gl i2/4 is differentially patterned in the somite, providing mechanisms f or differentially transducing the Sonic hedgehog signal to the myotoma l and sclerotomal lineages, Finally, we show that the activation of gl i2/4 is controlled by the process of somite formation and signals from the surface ectoderm, whereas upregulation of patched and activation of gli is controlled by the process of somite formation and a Sonic he dgehog signal, The Sonic hedgehog signal response genes, therefore, ha ve important functions in regulating the initiation of the Sonic hedge hog response in newly forming somites and in regulating the patterned expression of myoD and pax1 in the myotomal and sclerotomal lineages f ollowing somite formation.