Role of Serotonin and Catecholamines in Early Embryogenesis 

Several chemicals (neurotransmitters) which mediate nerve cell communication, including acetylcholine, serotonin, dopamine and norepinephrine, have been identified in both invertebrate and vertebrate embryos that have not yet developed a nervous system. The role of neurotransmitters in these preneural embryos is not understood. Results of studies from my lab and others suggest that these monoamines may regulate several basic developmental processes common to all animal embryos including cleavage, cell movements and cell shape changes, and cell differentiation (Brown and Anitole, 1993; Anitole and Brown, 2004).

In my lab we have used the sea urchin, Lytechinus pictus, embryo model to examine the role of serotonin and catecholamines in early embryogenesis.  Additionally, we are examining the potential pathways and receptors involved in these early developmental changes. 

Serotonin in early sea urchin embryogenesis

We have shown chemicals blocking central nervous system activity of serotonin in adult mammals will also inhibit sea urchin early gastrulation (Anitole et al., 1988b), a process which involves the inward folding of a layer of cells which will eventually form the walls of the gut tube. Furthermore, this inhibition can be reversed with serotonin and other agents which affect cyclic AMP and calcium ion levels (Anitole et al., 1988a). Binding of radiolabeled serotonin to whole cells (Brown and Shaver, 1989) and subcellular fractions (Brown and Shaver, 1987) has demonstrated the presence of intracellular serotonin binding sites in blastula and gastrula embryos and cell surface binding sites in post-gastrula embryos. From these studies and others we have postulated that serotonin initiates cell movements during early sea urchin gastrulation by interacting with intracellular receptors which are coupled to the cell cytoskeleton, either directly or via a signal transduction system involving cAMP and calcium ions.

We have completed an extensive analysis of the content of serotonin and catecholamines, and their precursors and metabolites in blastula, gastrula and post-gastrula embryos using high performance liquid chromatography with electrochemical detection (HPLC-EC) (Brown and Anitole, 1998; Anitole and Brown, 2004, Carroll et al., 2010). These studies are the first to definitively identify monoamines in these early embryos and support a role for serotonin (and norepinephrine) in the gastrulation process as suggested from our previous inhibitor and binding studies. We have also shown by RT-PCR analyses that the messenger RNA (mRNA) for tryptophan hydroxylase (serotonin synthetic enzyme) increases in embryos immediately prior to an increase in serotonin at gastrulation. We are currently examining the intraembryonic location of the mRNAs for tryptophan hydroxylase and the serotonin receptor, a molecule that mediates the action of serotonin in neurons, by in situ hybridization. These studies should allow us to determine if, as in mammalian neurons, the cells that synthesize serotonin are different from those that respond to it.