Independent Controls for Neocortical Neuron Production and Histogenetic Cell Death

Abstract

We estimated the proportion of cells eliminated by histogenetic cell death during the first 2 postnatal weeks in areas 1, 3 and 40 of the mouse parietal neocortex. For each layer and for the subcortical white matter in each neocortical area, the number of dying cells per mm² was calculated and the proportionate cell death for each day of the 2-week interval was estimated. The data show that cell death proceeds essentially uniformly across the neocortical areas and layers and that it does not follow either the spatiotemporal gradient of cell cycle progression in the pseudostratified ventricular epithelium of the cerebral wall, the source of neocortical neurons, or the ‘inside-out’ neocortical neuronogenetic sequence. Therefore, we infer that the control mechanisms of neocortical histogenetic cell death are independent of mechanisms controlling neuronogenesis or neuronal migration but may be associated with the ingrowth, expansion and a system-wide matching of neuronal connectivity.

Apaf-1-independent programmed cell death in mouse development

“…But, only a small percentage of the cells can be stained by TUNEL at a given time point. 28 Many neurons also undergo programmed cell death in the brain, but the reported number differs greatly among researchers, [29][30][31] probably due to the difficulty in detecting dead cells that are quickly eliminated. Here, we used DNase II-null mice to detect the programmed cell death that occurs during mouse embryogenesis.…”

A Novel Transient Glutamatergic Population Migrating from the Pallial–Subpallial Boundary Contributes to Neocortical Development

“…However, secretion of growth factors from signaling centers at the borders of the pallium during early stages of development and from ingrowing thalamic afferents during midcorticogenesis has been shown to provide an extrinsic control of neocortical growth (Dehay et al, 2001). In addition, an activity-dependent induction of programmed cell death (PCD) contributes to a specific refinement of the number of cortical neurons at early postnatal stages (Haydar et al, 1999;Verney et al, 2000). Nevertheless, the contribution of intrinsic versus extrinsic cues in the final output of corticogenesis remains an open question.…”

“…Nevertheless, a much higher number of transient cells and structures appear to exist as suggested by the observation of transient markers staining (Mitrovic and Schachner, 1996;Huh et al, 1997) and transient axonal projections (Innocenti and Price, 2005). Furthermore, up to 30% of cortical cells have been described to undergo apoptosis in the CP during the first 2 postnatal weeks in rodents (Ferrer et al, 1990;Haydar et al, 1999;Verney et al, 2000). Despite these observations, the existence, disappearance, and function of cortical transient cells have so far remained elusive because of the inability to label them throughout their life.…”

“…of the cells and to mainly occur around P4 -P6 in superficial layers (Verney et al, 2000). Indeed, the peak of PCD is commonly associated with increased sensory activity corresponding to the period of synaptogenesis and axonal outgrowth/targeting (Buss et al, 2006;Heck et al, 2008;Morishita and Hensch, 2008).…”

Final Technical Report

“…This death rate is based on the percentage of TUNEL+ neurons in the murine neocortex. During the prenatal period, normal cell death among neurons is rare, and Verney et al (51) determined that only 0.05% of cells are dying. However, researchers observed an increase to 0.9% on P5.…”