Role of the Protomap and Target-derived Signals in the Development of Intrahemispheric Connections

Mechanisms intrinsic to the early cerebral cortex have been implicated in the establishment of cortical area identity. However, the extent to which the cortical protomap contributes to the formation of highly complex intrahemispheric connections remains obscure. Mechanisms by which postmitotic neurons establish correct corticocortical connections later in corticogenesis also remain to be elucidated. Here, we used a new transplantation method, employing donor tissue harvested from enhanced green fluorescent protein-expressing rats, to show that cortical progenitors are regionally specified for connectional potential and that this controls the development of specific intrahemispheric projections. The acquisition of connectional capacity relies on positional cues within the cortical primordium, but is independent of thalamic inputs. In addition, since cortical neurons developing in organotypic slice culture extended axons more prominently into their normal cortical target tissues than into non-target tissues, we suggest that cortical neurons respond to specific signals derived from their cortical targets.