REGULATION OF NETRIN-1A EXPRESSION BY HEDGEHOG PROTEINS

Netrins, a family of growth cone guidance molecules, are expressed bot h in the ventral neural tube and in subsets of mesodermal cells. In an effort to better understand the regulation of netrins, we examined th e expression of netrin-1a in mutant cyclops, no tail, and floating hea d zebrafish embryos, in which axial midline structures are perturbed. Netrin-1a expression requires signals present in notochord and floor p late cells. In the myotome, but not the neural tube, netrin-1a express ion requires sonic hedgehog. In embryos lacking sonic hedgehog, the so nic-you locus, netrin-la expression is reduced or absent in the myotom es but present in the neural tube. Embryos lacking sonic hedgehog expr ess tiggy-winkle hedgehog in the floor plate, suggesting that, in the neural tube, tiggy-winkle hedgehog can compensate for the lack of soni c hedgehog in inducing netrin-1a expression. Ectopic expression of son ic hedgehog, tiggy-winkle hedgehog, or echidna hedgehog induces ectopi c netrin-la expression in the neural tube, and ectopic expression of s onic hedgehog or tiggy-winkle hedgehog, but not echidna hedgehog, indu ces ectopic netrin-1a expression in somites. These data demonstrate th at in vertebrates netrin-1a expression is regulated by Hedgehog signal ing.