Fates of the earliest generated cells in the developing murine neocortex

Abstract

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.

Prenatal carbon monoxide impairs migration of interneurons into the cerebral cortex

“…In untreated mice, BrdU+ cells after injection at E12 distributed in the bins closer to the white matter, and predominantly located in bins 8-10 (Fig. 2d), as predicted from prior studies (e.g., Price et al, 1997;Yozu et al, 2004). In CO exposed mice, a significant proportion of early born (E12) cells occurred in bin 7.…”

Disrupted ERK Signaling during Cortical Development Leads to Abnormal Progenitor Proliferation, Neuronal and Network Excitability and Behavior, Modeling Human Neuro-Cardio-Facial-Cutaneous and Related Syndromes

“…We examined the proportion of cells leaving the cell cycle by using a standard BrdU labeling protocol as previously described (Ormerod, 1997;Quinn et al, 2007). In the developing cortex, a single BrdU injection generates two distinctly labeled cell populations: (1) lightly labeled BrdUϩ cells that reentered the cell cycle and subsequently divided, generating two daughter cells; and (2) heavily labeled cells that are in S phase during BrdU administration and subsequently undergo terminal division (del Rio and Soriano, 1989;Gillies and Price, 1993;Price et al, 1997;Roy et al, 2004;Cubelos et al, 2008). The lightly labeled population accumulates with increasing length of BrdU exposure until a maximum is reached, as some cells reenter S phase and subsequently incorporate more BrdU (Fig.…”

Notch/Rbpjκ signaling regulates progenitor maintenance and differentiation of hypothalamic arcuate neurons

“…Development 140 (17) The regulation of progenitor cells through apoptosis is an important developmental event that occurs during the transition from neural progenitor to differentiated neuronal subtype (Blaschke et al, 1998;Price et al, 1997). In fact, loss of Notch signaling through Hes1 can induce apoptosis (Jensen et al, 2000;Raetzman et al, 2007).…”