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

Abstract

The generation of a precise number of neural cells and the determination of their laminar fate are tightly controlled processes during development of the cerebral cortex. Using genetic tracing in mice, we have identified a population of glutamatergic neurons generated by Dbx1-expressing progenitors at the pallial-subpallial boundary predominantly at embryonic day 12.5 (E12.5) and subsequent to Cajal-Retzius cells. We show that these neurons migrate tangentially to populate the cortical plate (CP) at all rostrocaudal and mediolateral levels by E14.5. At birth, they homogeneously populate cortical areas and represent Ͻ5% of cortical cells. However, they are distributed into neocortical layers according to their birthdates and express the corresponding markers of glutamatergic differentiation (Tbr1, ER81, Cux2, Ctip2). Notably, this population dies massively by apoptosis at the completion of corticogenesis and represents 50% of dying neurons in the postnatal day 0 cortex. Specific genetic ablation of these transient Dbx1-derived CP neurons leads to a 20% decrease in neocortical cell numbers in perinatal animals. Our results show that a previously unidentified transient population of glutamatergic neurons migrates from extraneocortical regions over long distance from their generation site and participates in neocortical radial growth in a non-cell-autonomous manner.

Adult pallium transcriptomes surprise in not reflecting predicted homologies across diverse chicken and mouse pallial sectors

“…A transient population of developing brain homeobox 1 (Dbx1) excitatory neurons migrates from the ventral pallium through the cortical subventricular zone, stimulating proliferative activity at embryonic stages. Subsequently, these Dbx1-positive neurons invade all cortical layers from the early postnatal period, but then largely disappear by adulthood (6,23). We thus favor the alternative explanation that this result is due to convergence of expression levels for genes that underlie common functional repertoires between nidopallium and neocortical layer IV.…”

Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain

“…Although early studies described tangential migration of presumed excitatory neurons in the embryonic cortex, they may have actually been describing tangentially migrating inhibitory neurons, which were discovered later (17). Interestingly, at least some rare (18), although usually transient (19,20), populations of excitatory cortical neurons migrate tangentially in the developing brain. Tangential migration of neural precursors in the developing hippocampus has previously only been observed in early postnatal developmental stages, during which the hippocampus is still immature and marked by ongoing growth and development (21,22).…”

A Wide Diversity of Cortical GABAergic Interneurons Derives from the Embryonic Preoptic Area

“…For example, Dbx1-expressing cells located in the septum and the VP give rise to two different populations of Cajal-Retzius cells that populate the surface of the cortex (Bielle et al, 2005). The VP also seems to give rise to a transient population of glutamatergic cells that migrate tangentially to the neocortex (Teissier et al, 2010(Teissier et al, , 2011. In addition, it has been shown that the Dbx1-expressing progenitor cells located in the POA give rise to a unique population of GABAergic interneurons that populate the amygdala (Hirata et al, 2009).…”

“…A small population of Dbx1-derived cortical GABAergic interneurons has also been recently identified (Teissier et al, 2010), but the origin and properties of these cells remain uncharacterized. To study this population of neurons, we crossed Dbx1 Cre mice with the reporter strain ROSA26 YFP (Srinivas et al, 2001) and analyzed the distribution of YFP-expressing cells in P30 mice.…”

“…Previous studies have shown that the pallial Dbx1-expressing domains (septum and VP) generate glutamatergic neurons, and therefore are unlikely to produce GABAergic interneurons (Bielle et al, 2005;Wonders and Anderson, 2006;Griveau et al, 2010;Teissier et al, 2010). Moreover, recent experimental evidence indicates that the subpallial septum is not a source of cortical GABAergic interneurons (Rubin et al, 2010).…”