Sequence of neuron origin and neocortical laminar fate: Relation to cell cycle of origin in the developing murine cerebral wall

Neurons destined for each region of the neocortex are known to arise approx imately in an "inside-to-outside" sequence from a pseudostratified ventricu lar epithelium (PVE). This sequence is initiated rostrolaterally and propag ates caudomedially. Moreover, independently of location in the PVE, the neu ronogenetic sequence in mouse is divisible into 11 cell cycles that occur o ver a 6 d period. Here we use a novel "birth hour" method that identifies s mall cohorts of neurons born during a single 2 hr period, i.e., 10-20% of a single cell cycle, which corresponds to similar to 1.5% of the 6 d neurono genetic period. This method shows that neurons arising with the same cycle of the 11 cycle sequence in mouse have common laminar fates even if they ar ise from widely separated positions on the PVE (neurons of fields 1 and 40) and therefore arise at different embryonic times. Even at this high level of temporal resolution, simultaneously arising cells occupy more than one c ortical layer, and there is substantial overlap in the distributions of cel ls arising with successive cycles. We demonstrate additionally that the lam inar representation of cells arising with a given cycle is little if at all modified over the early postnatal interval of histogenetic cell death. We infer from these findings that cell cycle is a neuronogenetic counting mech anism and that this counting mechanism is integral to subsequent processes that determine cortical laminar fate.