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 regulatory subunit mutant, we show that these hh activities are mediated by protein kinase A. The effects of dominant negative protein kinase A on pax2 expression appear to be cell nonautonomous, suggesting that cells can respond to regulation of hh signaling by modulating an additional cell-cell signaling pathway. We also investigate the potential involvement of cyclops in the hh signaling pathway and conclude that although cyclops mutant cells can respond to hh signaling, neither hh nor dominant negative protein kinase A rescues the phenotypes associated with cyclops.