THE ROLE OF THE CAMP PATHWAY IN MEDIATING THE EFFECT OF HEAD ACTIVATOR ON NERVE-CELL DETERMINATION AND DIFFERENTIATION IN HYDRA

In hydra, head activator (HA) acts as positive signal for nerve-cell d etermination and differentiation. For both events, HA uses cAMP as the second messenger. Evidence is presented that the cAMP agonist, Sp-cAM PS, is able to mimick the effect of HA on nerve-cell determination and differentiation and that it is blocked by the antagonist Rp-cAMP. An adenylyl cyclase associated protein, CAP, appears to be involved as me diator for transducing the signal from the transmembrane HA receptor t o the cAMP system. A cDNA coding for hydra CAP was isolated from the m ultiheaded mutant of Chlorohydra viridissima. The hydra CAP shows exte nsive homology with the yeast and, more so, mammalian CAPs. In hydra, CAP mRNA is expressed abundantly in interstitial and epithelial cells. The effect of HA, but not of cAMP, on nerve-cell differentiation was inhibited by pretreatment of hydra with a cap antisense oligonucleotid e, suggesting a role for CAP as mediator in the signal transduction ca scade between HA and cAMP.