INHIBITION OF PROTEIN-KINASE-A PHENOCOPIES ECTOPIC EXPRESSION OF HEDGEHOG IN THE CNS OF WILD-TYPE AND CYCLOPS MUTANT EMBRYOS

The zebrafish hedgehog (hh) family members tiggy-winkle hedgehog (twhh ) and sonic hedgehog (shh) are involved in patterning the ventral CNS and proximal eye. Using a dominant negative protein kinase A regulator y subunit mutant, we show that these hh activities are mediated by pro tein kinase A. The effects of dominant negative protein kinase A on pa x2 expression appear to be cell nonautonomous, suggesting that cells c an respond to regulation of hh signaling by modulating an additional c ell-cell signaling pathway. We also investigate the potential involvem ent of cyclops in the hh signaling pathway and conclude that although cyclops mutant cells can respond to hh signaling, neither hh nor domin ant negative protein kinase A rescues the phenotypes associated with c yclops. (C) 1996 Academic Press, Inc.