The timetable of laminar neurogenesis contributes to the specification of cortical areas in mouse isocortex.

In the primate visual cortex, the birthdate of neurons in homologous layers differ on either side of the 17-18 border suggesting that there might be different timetables of laminar histogenesis in these two areas (Dehay et al. [1993] Nature 366:464-466 and Kennedy et al. [1996] Soc. Neurosci. Abst. 22:525). Because of the potential importance of these findings for understanding mechanisms that generate areal identity, we have developed an experimental approach that makes it possible to accurately compute the timetable of laminar histogenesis from birthdating experiments. Here we report the results of an exhaustive examination of the tempo of layer production in five cortical areas of the mouse. Tritiated thymidine pulse injections were made during embryonic development and labeled neurons were examined in three frontoparietal areas (areas 3, 4, and 6) and two occipital areas (areas 17 and 18a) of the adult cortex. The correlation between the radial distribution of neurons and the intensities of labeling enabled us to reliably identify first generation neurons (i.e., those neurons that quit the cell-cycle in the first round of mitosis after injection). For each cortical layer, the percentage of first generation neurons with respect to the total number of neurons defined a laminar labeling index. Changes of the laminar labeling index over time determined the timetable of layer formation. The onset and duration of layer formation was identical in the two occipital areas. This finding contrasted with the frontoparietal areas where there were important differences in the timing of infragranular and granular layer formation and noticeably production of layers VIa, V, and IV occurs earlier in area 3 than in area 6. The timing of laminar production of areas 17 and 18a resembles more that of area 3 than that of area 6. With respect to areas 3 and 6, area 4 shows an intermediate but significantly different timetable of layer production. These marked areal differences in the timetable of laminar histogenesis contrasted with the relative homogeneity within areas so that we have been able to demonstrate that the interareal differences are not merely the expression of known neurogenic gradients. These results suggest that in the mouse frontoparietal isocortex, neighbouring regions of the ventricular zone that will give rise to distinct areas follow distinct programs of layer production. These areal differences occur before thalamic innervation and suggest an early regionalisation of laminar histogenesis.