Influence of dopamine on precursor cell proliferation and differentiation in the embryonic mouse telencephalon.

Dopamine and its receptor binding sites appear in the brain early in the embryonic period raising the possibility that dopamine may influence brain development. We show that one component of dopamine's role in brain development is its ability to influence proliferation and differentiation of progenitor cells in the neostriatum and the dorsomedial prefrontal cortex on embryonic day 15 in mice. Dopamine and a D1-like receptor agonist reduce the relative proportion of progenitor cells incorporating the S phase marker bromodeoxyuridine. A D2-like agonist produces the opposite effect. Both the effects are evident in the lateral ganglionic eminence, neuroepithelial precursor of the neostriatum and in the neuroepithelium of the dorsomedial prefrontal cortex. Neostriatal progenitor cells are more responsive than cortical progenitor cells to the effects of dopamine receptor activation. Furthermore, progenitor cells in the ventricular zone are more responsive to D1-like agonists and progenitors in the subventricular zone more so to D2-like agonists. Thus, dopamine's developmental effects show regional and progenitor cell type specificity, presumably due to heterogeneity in the distribution of its receptor binding sites.