Roles for serotonin in neuroembryogenesis.

Possible non-transmitter roles for 5-HT in different phases of early neuroembryogenesis have been discussed based upon experimental evidence from the rat and chick. Fluorescence histochemical studies have demonstrated sites of uptake and synthesis of 5-HT in the chick embryo during the first few days of incubation. These sites are located in discrete regions of the notochord and floor plate of the neural tube as well as in extra-neural regions such as the somites and primitive gut. The 5-HT patterns are distinctly different from those observed for the uptake and synthesis of norepinephrine in embryos of the same age. Spatio-temporal changes in the distribution of these sites during closure of the neural tube suggest a role for 5-HT in various aspects of neural tube development. Moreover, the non-overlapping localization of 5-HT and norepinephrine raises the possibility that these two amines may exert different and perhaps cooperative influences on early neurogenic processes in the chick. In the rat, autoradiographic and biochemical studies concerning the consequences of 5-HT depletion in the embryo for development of different brain regions have provided evidence that 5-HT acts as a "differentiation signal" regulating the time of neuronal genesis in those cell populations which will eventually receive 5-HT innervation. Although the details of this system are as yet unknown, these studies suggest that 5-HT (and possibly the other monoamine transmitters) may actually "mold" the construction of their own circuitry during neurogenesis. Further, the ability of drugs and stress to interact with this process during that period of gestation when the monoamines are required as humoral signals suggests that maternal influences can interfere with ontogeny of this circuitry during pre- and possibly postnatal development. It is not yet clear whether the data in chicks and rats can be directly analogized from the one species to the other. Nevertheless, the evidence that sites of 5-HT uptake and/or synthesis are present during the earliest phases of neurogenesis in the chick and the observation that 5-HT depletion can alter the time of genesis of 5-HT target cells in the rat provide a new context for the consideration of possible actions of 5-HT prior to its role as a neurotransmitter substance.