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

GABA-containing (GABAergic) interneurons comprise a very heterogeneous group of 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 two main regions, the medial and the caudal ganglionic eminences (MGE and CGE, respectively). In addition, it has been shown that 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 CGE-derived 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 the mechanisms controlling 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 mous

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

GABA-containing (GABAergic) interneurons comprise a very heterogeneous group of 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 two main regions, the medial and the caudal ganglionic eminences (MGE and CGE, respectively). In addition, it has been shown that 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 CGE-derived 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 the mechanisms controlling 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.Fil: Gelman, Diego Matias. Universidad Miguel Hernández; España. Consejo Superior de Investigaciones Cientificas. Instituto de Neurociencia de Alicante; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Griveau, Amelie. Universite Paris Diderot - Paris 7; FranciaFil: Dehorter, Nathalie. Consejo Superior de Investigaciones Cientificas. Instituto de Neurociencia de Alicante; España. Universidad Miguel Hernández; EspañaFil: Teissier, Anne. Universite Paris Diderot - Paris 7; FranciaFil: Varela, Carolina. Consejo Superior de Investigaciones Cientificas. Instituto de Neurociencia de Alicante; España. Universidad Miguel Hernández; EspañaFil: Pla, Ramon. Consejo Superior de Investigaciones Cientificas. Instituto de Neurociencia de Alicante; España. Universidad Miguel Hernández; EspañaFil: Pierani, Alessandra. Universite Paris Diderot - Paris 7; FranciaFil: Marin, Oscar. Consejo Superior de Investigaciones Cientificas. Instituto de Neurociencia de Alicante; España. Universidad Miguel Hernández; Españ

Identification of Multiple Subsets of Ventral Interneurons and Differential Distribution along the Rostrocaudal Axis of the Developing Spinal Cord

The spinal cord contains neuronal circuits termed Central Pattern Generators (CPGs) that coordinate rhythmic motor activities. CPG circuits consist of motor neurons and multiple interneuron cell types, many of which are derived from four distinct cardinal classes of ventral interneurons, called V0, V1, V2 and V3. While significant progress has been made on elucidating the molecular and genetic mechanisms that control ventral interneuron differentiation, little is known about their distribution along the antero-posterior axis of the spinal cord and their diversification. Here, we report that V0, V1 and V2 interneurons exhibit distinct organizational patterns at brachial, thoracic and lumbar levels of the developing spinal cord. In addition, we demonstrate that each cardinal class of ventral interneurons can be subdivided into several subsets according to the combinatorial expression of different sets of transcription factors, and that these subsets are differentially distributed along the rostrocaudal axis of the spinal cord. This comprehensive molecular profiling of ventral interneurons provides an important resource for investigating neuronal diversification in the developing spinal cord and for understanding the contribution of specific interneuron subsets on CPG circuits and motor control

Dbx1-Expressing Cells Are Necessary for the Survival of the Mammalian Anterior Neural and Craniofacial Structures

Development of the vertebrate forebrain and craniofacial structures are intimately linked processes, the coordinated growth of these tissues being required to ensure normal head formation. In this study, we identify five small subsets of progenitors expressing the transcription factor dbx1 in the cephalic region of developing mouse embryos at E8.5. Using genetic tracing we show that dbx1-expressing cells and their progeny have a modest contribution to the forebrain and face tissues. However, their genetic ablation triggers extensive and non cell-autonomous apoptosis as well as a decrease in proliferation in surrounding tissues, resulting in the progressive loss of most of the forebrain and frontonasal structures. Targeted ablation of the different subsets reveals that the very first dbx1-expressing progenitors are critically required for the survival of anterior neural tissues, the production and/or migration of cephalic neural crest cells and, ultimately, forebrain formation. In addition, we find that the other subsets, generated at slightly later stages, each play a specific function during head development and that their coordinated activity is required for accurate craniofacial morphogenesis. Our results demonstrate that dbx1-expressing cells have a unique function during head development, notably by controlling cell survival in a non cell-autonomous manner

Dynamic Assignment and Maintenance of Positional Identity in the Ventral Neural Tube by the Morphogen Sonic Hedgehog

During development of the vertebrate neural tube, cells acquire their positional identity from not only the spatial level of the Sonic Hedgehog signaling gradient, but also the temporal duration

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

A Mammalian Conserved Element Derived from SINE Displays Enhancer Properties Recapitulating Satb2 Expression in Early-Born Callosal Projection Neurons

Short interspersed repetitive elements (SINEs) are highly repeated sequences that account for a significant proportion of many eukaryotic genomes and are usually considered “junk DNA”. However, we previously discovered that many AmnSINE1 loci are evolutionarily conserved across mammalian genomes, suggesting that they may have acquired significant functions involved in controlling mammalian-specific traits. Notably, we identified the AS021 SINE locus, located 390 kbp upstream of Satb2. Using transgenic mice, we showed that this SINE displays specific enhancer activity in the developing cerebral cortex. The transcription factor Satb2 is expressed by cortical neurons extending axons through the corpus callosum and is a determinant of callosal versus subcortical projection. Mouse mutants reveal a crucial function for Sabt2 in corpus callosum formation. In this study, we compared the enhancer activity of the AS021 locus with Satb2 expression during telencephalic development in the mouse. First, we showed that the AS021 enhancer is specifically activated in early-born Satb2+ neurons. Second, we demonstrated that the activity of the AS021 enhancer recapitulates the expression of Satb2 at later embryonic and postnatal stages in deep-layer but not superficial-layer neurons, suggesting the possibility that the expression of Satb2 in these two subpopulations of cortical neurons is under genetically distinct transcriptional control. Third, we showed that the AS021 enhancer is activated in neurons projecting through the corpus callosum, as described for Satb2+ neurons. Notably, AS021 drives specific expression in axons crossing through the ventral (TAG1−/NPY+) portion of the corpus callosum, confirming that it is active in a subpopulation of callosal neurons. These data suggest that exaptation of the AS021 SINE locus might be involved in enhancement of Satb2 expression, leading to the establishment of interhemispheric communication via the corpus callosum, a eutherian-specific brain structure

Cerebral cortex development: From progenitors patterning to neocortical size during evolution.

International audienceThe central nervous system is composed of thousands of distinct neurons that are assembled in a highly organized structure. In order to form functional neuronal networks, distinct classes of cells have to be generated in a precise number, in a spatial and temporal hierarchy and to be positioned at specific coordinates. An exquisite coordination of appropriate growth of competent territories and their patterning is required for regionalization and neurogenesis along both the anterior-posterior and dorso-ventral axis of the developing nervous system. The neocortex represents the brain territory that has undergone a major increase in its relative size during the course of mammalian evolution. In this review we will discuss how the fine tuning of growth and cell fate patterning plays a crucial role in the achievement of the final size of central nervous system structures and how divergence might have contributed to the surface increase of the cerebral cortex in mammals. In particular, we will describe how lack of precision might have been instrumental to neocortical evolution

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

Quand la migration de neurones signalisateurs contrôle la régionalisation du cortex cérébral

International audienc