A Novel Role for Dbx1-Derived Cajal-Retzius Cells in Early Regionalization of the Cerebral Cortical Neuroepithelium

Patterning of the cerebral cortex during embryogenesis depends not only on passive diffusion of morphogens but also on signal delivery by Cajal-Retzius neurons that migrate over long distances

Cractérisation et fonction des cellulesde Cajal-Retzius dérivées de Dbx1 lors du développement du cortex cérébral

Notre premier travail porte sur la théorie des classes de Chern pour les faisceaux cohérents. Sur les variétés projectives, elle est complètement achevée dans les anneaux de Chow grâce à l'existence de résolutions globales localement libres et se ramène formellement à la théorie pour les fibrés. Un résultat de Voisin montre que ce résolutions n'existent pas toujours sur des variétés complexes compactes générales. Nous construisons ici par récurrence sur la dimension de la variété de base des classes de Chern en cohomologie de Deligne rationnelle pour les faisceaux cohérents en imposant la formule de Grothendieck-Riemann-Roch pour les immersions et en utilisant des méthodes de dévissage. Ces classes sont les seules à vérifier la formule de fonctorialité par pull-back, la formule de Whitney et GRR pour les immersions; elles coïncident donc avec les classes topologiques et les classes d'Atiyah. Elles vérifient aussi GRR pour les morphismes projectifs. Notre second travail est l'étude des schémas de Hilbert ponctuels d'une variété symplectique ou presque-complexe de dimension 4. Ils ont été construits par Voisin et généralisent les schémas de Hilbert connus pour les surfaces projectives. En utilisant les structures complexes relatives intégrables introduites dans la construction de Voisin, nous pouvons étendre au cas presque-complexe ou symplectique la théorie classique. Nous calculons les nombres de Betti, nous construisons les opérateurs de Nakajima, nous étudions l'anneau de cohomologie de ces schémas de Hilbert et nous prouvons dans ce contexte un cas particulier de la conjecture de la résolution crêpante de Ruan.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

A wide diversity of cortical GABAergic interneurons derives from the embryonic preoptic area

GABA-containing (GABAergic) interneurons comprise a very heterogeneousgroupof cells that are crucial for cortical function. Different classes of interneurons specialize in targeting specific subcellular domains of excitatory pyramidal cells or other interneurons, which provides cortical circuits with an enormous capability for information processing. As in other regions of the CNS, cortical interneuron diversity is thought to emerge from the genetic specification of different groups of progenitor cells within the subpallium. Most cortical interneurons originate from twomainregions, the medial and the caudal ganglionic eminences(MGEand CGE, respectively). In addition, it has beenshownthat progenitors in the embryonic preoptic area (POA) also produce a small population of cortical GABAergic interneurons. Here, we show that the contribution of the POA to the complement of cortical GABAergic interneurons is larger than previously believed. Using genetic fate mapping and in utero transplantation experiments, we demonstrate that Dbx1-expressing progenitor cells in the POA give rise to a small but highly diverse cohort of cortical interneurons, with some neurochemical and electrophysiological characteristics that were previously attributed to MGE- or CGEderived interneurons. There are, however, some features that seem to distinguish POA-derived interneurons from MGE- or CGE-derived cells, such as their preferential laminar location. These results indicate that themechanismscontrolling the specification of different classes of cortical interneurons might be more complex than previously expected. Together with earlier findings, our results also suggest that the POA generates nearly 10% of the GABAergic interneurons in the cerebral cortex of the mouse. © 2011 the authors.This work was supported by grants from the European Commission through STREP contract number 005139 (INTERDEVO) to O.M. and A.P.; the Spanish Ministry of Science and Innovation SAF2008-00770, SAF2009-08049-E, and CONSOLIDER CSD2007-00023 to O.M.; and Fondation pour le Recherche Médicale (INE20060306503) and Ville de Paris (2006 ASES 102) to A.P. D.G. was recipient of a Marie Curie International Incoming Fellowship.Peer Reviewe

A novel transient glutamatergic population migrating from the pallial-subpallial boundary contributes to neocortical development.

International audienceThe 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 <5% 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

Enhanced Abventricular Proliferation Compensates Cell Death in the Embryonic Cerebral Cortex

International audienc

Loss of Pla2r1 decreases cellular senescence and age‐related alterations caused by aging and Western diets

International audienceCellular senescence is induced by many stresses including telomere shortening, DNA damage, oxidative, or metabolic stresses. Senescent cells are stably cell cycle arrested and they secrete many factors including cytokines and chemokines. Accumulation of senescent cells promotes many age‐related alterations and diseases. In this study, we investigated the role of the pro‐senescent phospholipase A2 receptor 1 (PLA2R1) in regulating some age‐related alterations in old mice and in mice subjected to a Western diet, whereas aged wild‐type mice displayed a decreased ability to regulate their glycemia during glucose and insulin tolerance tests, aged Pla2r1 knockout (KO) mice efficiently regulated their glycemia and displayed fewer signs of aging. Loss of Pla2r1 was also found protective against the deleterious effects of a Western diet. Moreover, these Pla2r1 KO mice were partially protected from diet‐induced senescent cell accumulation, steatosis, and fibrosis. Together these results support that Pla2r1 drives several age‐related alterations, especially in the liver, arising during aging or through a Western diet

Multiple origins of Cajal-Retzius cells at the borders of the developing pallium

Cajal-Retzius cells are critical in cortical lamination, but very little is known about their origin and development. The homeodomain transcription factor Dbx1 is expressed in restricted progenitor domains of the developing pallium: the ventral pallium (VP) and the septum. Using genetic tracing and ablation experiments in mice, we show that two subpopulations of Reelin(+) Cajal-Retzius cells are generated from Dbx1-expressing progenitors. VP- and septum-derived Reelin(+) neurons differ in their onset of appearance, migration routes, destination and expression of molecular markers. Together with reported data supporting the generation of Reelin(+) cells in the cortical hem, our results show that Cajal-Retzius cells are generated at least at three focal sites at the borders of the developing pallium and are redistributed by tangential migration. Our data also strongly suggest that distinct Cajal-Retzius subtypes exist and that their presence in different territories of the developing cortex might contribute to region-specific properties