Pattern formation in the developing mammalian forebrain: selective adhesion of early but not late postmitotic...

The mammalian cerebral cortex and striatum exhibit spatially restricted distributions of neurons. These neuronal collectives correlate with the age at which the neurons become postmitotic. We investigated in vitro the role of cell adhesion in the organization of like-birthdated neurons within the rat telencephalon. Specifically, the ability of neurons of similar birthdate to reassociate with one another within either striatal or cortical reaggregates was observed. Early postmitotic neurons (destined for the striatal patch compartment and cortical deep layers) or later born neurons (destined for the striatal matrix compartment and cortical superficial layers) were labeled in vivo with [3H]-thymidine or bromodeoxyuridine (Brdu) on Embryonic Day (E) 13 or 18, respectively. Two or seven days later, the striatum and cortex were separately removed, dissociated, and reaggregated in suspension cultures for 5 days. Within both striatal and cortical reaggregates, E13 [3H]thymidine-labeled cells were observed to clump together toward the center of the reaggregates. Conversely, reaggregates containing cells labeled on E18 with a single [3H]thymidine injection or with two separate Brdu injections contained labeled cells which were dispersed with respect to each other, but showed an overall distribution toward the periphery of the reaggregates. These results suggest that early, but not late, postmitotic striatal and cortical neurons selectively associate with one another within their respective structures. Dissociated embryonic striatal and cortical neurons were then co-reaggregated to examine if a single adhesive mechanism is shared by both tissues. Early born neurons within these reaggregates clustered with each other regardless of tissue type. Later born cortical and striatal neurons were found dispersed in relation to each other and the early born neurons. However, the selective adhesion of early born striatal and cortical neurons is not an attribute of all early postmitotic forebrain neurons, because dissociated early born septal-basal forebrain neurons were found dispersed within reaggregates of septal-basal forebrain tissue or when cocultured with striatal tissue. These results suggest that the organization of cortical and striatal neuronal groups may depend on a common adhesive mechanism that crosses tissue-type boundaries.