Competitive outgrowth of neural processes arising from long-distance cAMP signaling

During development, competition among undifferentiated neurites results in the growth of one neurite at the expense of the rest. This neurite becomes the axon. A similar competitive mechanism later governs the differential outgrowth of the axon and its branches. A long-range signal between different parts of the neuron is required to mediate this competition, but the nature of this signal was unknown. Recent work has shown that local cyclic adenosine monophosphate (cAMP) signaling promotes neurite growth but leads to decreased cAMP concentrations in distant neurites, thereby inhibiting their growth. The precise mechanism mediating long-distance cyclic nucleotide signaling is unclear but may involve localized calcium transients and autocrine signaling. Mutually inhibitory, competitive interactions during outgrowth of neural processes can emerge from these signaling events, both during axon specification and later during axon branching.