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 l ayers differ on either side of the 17-18 border suggesting that there might be different timetables of laminar histogenesis in these two are as (Dehay et al. [1993] Nature 366:464-466 and Kennedy et al. [1996] S ec. Neurosci. Abst. 22:525). Because of the potential importance of th ese 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 birthda ting experiments. Here we report the results of an exhaustive examinat ion of the tempo of layer production in five cortical areas of the mou se. Tritiated thymidine pulse injections were made during embryonic de velopment and labeled neurons were examined in three frontoparietal ar eas (areas 3, 4, and 6) and two occipital areas (areas 17 and 18a) of the adult cortex. The correlation between the radial distribution of n eurons and the intensities of labeling enabled us to reliably identify first generation neurons (i.e., those neurons that quit the cell-cycl e in the first round of mitosis after injection). For each cortical la yer, the percentage of first generation neurons with respect to the to tal number of neurons defined a laminar labeling index. Changes of the laminar labeling index over time determined the timetable of layer fo rmation. The onset and duration of layer formation was identical in th e two occipital areas. This finding contrasted with the frontoparietal areas where there were important differences in the timing of infragr anular and granular layer formation and noticeably production of layer s VIa, V, and IV occurs earlier in area 3 than in area 6. The timing o f 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 i ntermediate but significantly different timetable of layer production. These marked areal differences in the timetable of laminar histogenes is contrasted with the relative homogeneity within areas so that we ha ve been able to demonstrate that the interareal differences are not me rely the expression of known neurogenic gradients. These results sugge st that in the mouse frontoparietal isocortex, neighbouring regions of the ventricular zone that will give rise to distinct areas follow dis tinct programs of layer production. These areal differences occur befo re thalamic innervation and suggest an early regionalisation of lamina r histogenesis. (C) 1997 Wiley-Liss, Inc.