Fates of the earliest generated cells in the developing murine neocortex.

In mammalian species studied to date, the first-born neocortical cells normally form two layers, one above and one below the cortical plate, called the marginal zone (future layer 1) and the subplate. In primates and carnivores, many of these first-born cells die early in postnatal life. Whether this also occurs in rodents is highly controversial. In this study, we injected pregnant mice with bromodeoxyuridine on embryonic days (E) 11-14 to label the earliest generated neocortical cells, and examined their fates between birth and postnatal day 21. At birth, most cells born on embryonic day 11 were below the cortical plate, and a smaller proportion were above it. Very few of these cells remained by postnatal day 3 and there were none at any depth in the neocortex at older ages. At birth, the largest proportion of cells born on embryonic days 12 and 13 were in the subplate and smaller proportions were in the cortical plate and marginal zone. At older ages, almost all of these cells had disappeared from the marginal zone and from below the cortical plate, although some were retained in the cortical plate. The density of the remaining E12- and E13-born cells decreased more than could be explained by neocortical expansion alone. As a control, we studied cells born on embryonic day 14. These cells were restricted to the cortical plate at birth. By postnatal day 21, their density had decreased by an amount that could be explained by neocortical expansion alone. We conclude that, as in other species, many of the earliest generated cells of the murine neocortex die.