Alpha 2A-adrenergic receptors are expressed by diverse cell types in the fetal primate cerebral wall

The cellular elements of the fetal monkey cerebral wall expressing alpha 2A, the most common subtype of the alpha 2 receptor class, were examined by using nonisotopic in situ hybridization and immunohistochemistry with double-labeling for cell type-specific markers. At the three embryonic ages examined, E70, E90, and E120, alpha 2A receptors were expressed throughout the embryonic cerebral wall. In the E70 and E90 fetuses, alpha 2A receptors were observed in most cells of the proliferative zones. Some alpha 2A-positive cells also expressed a proliferation-associated antigen, Ki-67, suggesting that the receptors are present in dividing cells. Furthermore, at E90, alpha 2A receptors were detected on fibers passing between the ventricular and subventricular proliferative zones. At all ages studied, alpha 2A receptors were expressed by migrating neurons in the intermediate zone, characterized by a spindle-like shape, radial alignment, and close association with radial glia. alpha 2A receptors were also expressed by postmigrational microtubule-associated protein-2-positive neurons of the intermediate and subplate zones and the cortical plate. In the marginal zone, alpha 2A receptors were present in the Cajal-Retzius neurons. Finally, alpha 2A receptors were seen in the glial fibrillary acidic protein-positive cells at all ages studied. In addition, dopamine-beta-hydroxylase immunohistochemistry, employed to determine the potential source of noradrenaline in the embryonic cerebral wall, revealed noradrenergic innervation in the marginal, subplate, and intermediate zones of the monkey occipital lobe as early as E70. Based on our observations and available data on alpha 2A signal transduction pathways, we propose that these receptors are involved in regulating the generation, migration, and maturation of cerebral cortical cells.