Neural induction is mediated by cross-talk between the protein kinase C and cyclic AMP pathways.

Embryonic inductions appear to be mediated by the concerted action of different inducing factors that modulate one another's activity. Such modulation is likely to reflect interactions between the signal transduction pathways through which the inducing factors act. We tested this idea for the induction of neural tissue. We report that both adenylate cyclase activity and cAMP concentration increase substantially in induced neuroectoderm during neural induction. The enhancement of adenylate cyclase activity requires protein kinase C (PKC) activation, indicating cross-talk between these two signal transduction pathways. This cross-talk appears to be essential for neural induction. Whereas cAMP analogs alone were not neural inducers, they had a synergistic inducing effect if ectoderm was first incubated with TPA (12-O-tetradecanoylphorbol 13-acetate), a PKC activator. These results strongly suggest that at least two signals mediate neural induction. The first signal activates PKC and the second signal then activates the cAMP pathway effectively.