Perlecan controls neurogenesis in the developing telencephalon

BACKGROUND: Perlecan is a proteoglycan expressed in the basal lamina of the neuroepithelium during development. Perlecan absence does not impair basal lamina assembly, although in the 55% of the mutants early disruptions of this lamina conducts to exencephaly, impairing brain development. The rest of perlecan-null brains complete its prenatal development, maintain basal lamina continuity interrupted by some isolated ectopias, and are microcephalic. Microcephaly consists of thinner cerebral walls and underdeveloped ganglionic eminences. We have studied the mechanisms that generate brain atrophy in telencephalic areas where basal lamina is intact. RESULTS: Brain atrophy in the absence of perlecan started in the ventral forebrain and extended to lateral and dorsal parts of the cortex in the following stages. First, the subpallial forebrain developed poorly in early perlecan-null embryos, because of a reduced cell proliferation: the number of cells in mitosis decreased since the early stages of development. This reduction resulted in a decreased tangential migration of interneurons to the cerebral cortex. Concomitant with the early hypoplasia observed in the medial ganglionic eminences, Sonic Hedgehog signal decreased in the perlecan-null floor plate basal lamina at E12.5. Second, neurogenesis in the pallial neuroepithelium was affected in perlecan deficient embryos. We found reductions of nearly 50% in the number of cells exiting the cell cycle at E12–E13. The labeling index, which was normal at this age, significantly decreased with advancing corticogenesis. Moreover, nestin(+ )or PCNA(+ )progenitors increased since E14.5, reaching up to about 150% of the proportion of PCNA(+ )cells in the wild-type at E17.5. Thus, labeling index reduction together with increased progenitor population, suggests that atrophy is the result of altered cell cycle progression in the cortical progenitors. Accordingly, less neurons populated the cortical plate and subplate of perlecan-null neocortex, as seen with the neuronal markers β-tubulin and Tbr1. CONCLUSION: As a component of the basal lamina, perlecan both maintains this structure and controls the response of the neuroepithelium to growth factors. Less mitotic cells in the early medial ganglionic eminences, and impaired cell cycle progression in the late neocortex, suggests insufficient recruitment and signaling by neurogenic morphogens, such as SHH or FGF2

Two Separate Subtypes of Early Non-Subplate Projection Neurons in the Developing Cerebral Cortex of Rodents

The preplate of the cerebral cortex contains projection neurons that connect the cortical primordium with the subpallium. These are collectively named pioneer neurons. After preplate partition, most of these pioneer neurons become subplate neurons. Certain preplate neurons, however, never associate with the subplate but rather with the marginal zone. In the present overview, we propose a novel classification of non-subplate pioneer neurons in rodents into two subtypes. In rats, the neurons of the first subtype are calbindin+ (CB), calretinin+ (CR) and L1+ and are situated in the upper part of the preplate before its partition. Neurons of the second subtype are TAG-1+ and are located slightly deeper to the previous population in the preplate. After the preplate partition, the CB+, CR+ and L1+ neurons remain in the marginal zone whereas TAG-1+ neurons become transiently localized in the upper cortical plate. In mice, by contrast, calcium binding proteins did not label pioneer neurons. We define in mice two subtypes of non-subplate pioneer neurons, either L1+ or TAG-1+/cntn2+. We propose these to be the homologues of the two subtypes of non-subplate pioneer neurons of rats. The anatomical distribution of these neuron populations is similar in rats and mice. The two populations of non-subplate pioneer neurons differ in their axonal projections. Axons of L1+ pioneer neurons project to the ganglionic eminences and the anterior preoptic area, but avoid entering the posterior limb of the internal capsule towards the thalamus. Axons of TAG-1+ pioneer neurons project to the lateral parts of the ganglionic eminences at the early stages of cortical histogenesis examined

Neural cell adhesion molecule, NCAM, regulates thalamocortical axon pathfinding and the organization of the cortical somatosensory representation in mouse

To study the potential role of neural cell adhesion molecule (NCAM) in the development of thalamocortical (TC) axon topography, wild type, and NCAM null mutant mice were analyzed for NCAM expression, projection, and targeting of TC afferents within the somatosensory area of the neocortex. Here we report that NCAM and its α-2,8-linked polysialic acid (PSA) are expressed in developing TC axons during projection to the neocortex. Pathfinding of TC axons in wild type and null mutant mice was mapped using anterograde DiI labeling. At embryonic day E16.5, null mutant mice displayed misguided TC axons in the dorsal telencephalon, but not in the ventral telencephalon, an intermediate target that initially sorts TC axons toward correct neocortical areas. During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM null mutant animals. NCAM null mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex. As shown by Nissl and cytochrome oxidase staining, barrels of the anterolateral barrel subfield (ALBSF) and the most distal barrels of the posteromedial barrel subfield (PMBSF) did not segregate properly in null mutant mice. These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex

Cortical GABAergic Neurons: Stretching it Remarks, Main Conclusions and Discussion

18 p., 1 figure and references.The articles in this Special Topic cover a range of issues concerning long-distance projecting cortical GABAergic neurons, in the context of interneuron diversity. As several authors report, these neurons are attracting renewed attention spurred by new techniques and markers which show great potential for deciphering their role in cortical organization and microcircuitry. Other authors have emphasized developmental origins of particular subpopulations and their roles in early cortical circuitry. Notable recurring themes are species-specifi c features and probable implications for normal and pathological cortical functioning. A corollary theme, evident in many of these articles, concerns nomenclature. Several terms are almost interchangeably used, but nevertheless distinct; that is: subplate, layer 7, layer VIB, pioneer and interstitial neuron (see comments to follow Clancy et al., below, among others). In this article the main conclusions, and some of what the host editors (Kathleen Rockland and Javier DeFelipe) consider the most interesting remarks, have been extracted from each of the individual articles. These commentaries are not necessarily directly derived from the original work of the authors, and may be the result of the collective work of several different laboratories. This is followed by a section dedicated to more general comments and a discussion of the issues raised. The authors who have participated in this article are listed in alphabetical order.Peer reviewe

Tracking the weathering of basalts on Mars using lithium isotope fractionation models

An edited version of this paper was published by AGU. Copyright (2015) American Geophysical UnionLithium (Li), the lightest of the alkali elements, has geochemical properties that include high aqueous solubility (Li is the most fluid mobile element) and high relative abundance in basalt-forming minerals (values ranking between 0.2 and 12 ppm). Li isotopes are particularly subject to fractionation because the two stable isotopes of lithium - 7Li and 6Li - have a large relative mass difference (∼15%) that results in significant fractionation between water and solid phases. The extent of Li isotope fractionation during aqueous alteration of basalt depends on the dissolution rate of primary minerals - the source of Li - and on the precipitation kinetics, leading to formation of secondary phases. Consequently, a detailed analysis of Li isotopic ratios in both solution and secondary mineral lattices could provide clues about past Martian weathering conditions, including weathering extent, temperature, pH, supersaturation, and evaporation rate of the initial solutions in contact with basalt rocks. In this paper, we discuss ways in which Martian aqueous processes could have lead to Li isotope fractionation. We show that Li isotopic data obtained by future exploration of Mars could be relevant to highlighting different processes of Li isotopic fractionation in the past, and therefore to understanding basalt weathering and environmental conditions early in the planet's historyData supporting our models and calculations are available as supporting information. The research leading to these results is a contribution from the Project ‘icyMARS’’, funded by the European Research Council, Starting Grant no 307496. This work was also partially supported by the European FEDER program and the Spanish Ministry of Science (MICINN) through the project CGL2011–30079. Comments by R. James and four anonymous reviewers helped us to clarify and strengthen our wor

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus

Lateral thalamic eminence – a novel origin for mGluR1/lot cells

A unique population of cells, called "lot cells," circumscribes the path of the lateral olfactory tract (LOT) in the rodent brain and acts to restrict its position at the lateral margin of the telencephalon. Lot cells were believed to originate in the dorsal pallium (DP). We show that Lhx2 null mice that lack a DP show a significant increase in the number of mGluR1/lot cells in the piriform cortex, indicating a non-DP origin of these cells. Since lot cells present common developmental features with Cajal-Retzius (CR) cells, we analyzed Wnt3a- and Dbx1-reporter mouse lines and found that mGluR1/lot cells are not generated in the cortical hem, ventral pallium, or septum, the best characterized sources of CR cells. Finally, we identified a novel origin for the lot cells by combining in utero electroporation assays and histochemical characterization. We show that mGluR1/lot cells are specifically generated in the lateral thalamic eminence and that they express mitral cell markers, although a minority of them express DeltaNp73 instead. We conclude that most mGluR1/lot cells are prospective mitral cells migrating to the accessory olfactory bulb (OB), whereas mGluR1+, DeltaNp73+ cells are CR cells that migrate through the LOT to the piriform cortex and the OB

The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala

In rodents, the medial nucleus of the amygdala receives direct inputs from the accessory olfactory bulbs and is mainly implicated in pheromone-mediated reproductive and defensive behaviors. The principal neurons of the medial amygdala are GABAergic neurons generated principally in the caudo-ventral medial ganglionic eminence and preoptic area. Beside GABAergic neurons, the medial amygdala also contains glutamatergic Otp-expressing neurons cells generated in the lateral hypothalamic neuroepithelium and a non-well characterized Pax6-positive population. In the present work, we describe a novel glutamatergic Ebf3-expressing neuronal subpopulation distributed within the periphery of the postero-ventral medial amygdala. These neurons are generated in a pallial domain characterized by high expression of Gdf10. This territory is topologically the most caudal tier of the ventral pallium and accordingly, we named it Caudo-Ventral Pallium (CVP). In the absence of Pax6, the CVP is disrupted and Ebf3-expressing neurons fail to be generated. Overall, this work proposes a novel model of the neuronal composition of the medial amygdala and unravels for the first time a new novel pallial subpopulation originating from the CVP and expressing the transcription factor Ebf3.This work was supported by Grants of the French National Research Agency (Agence Nationale de la Recherche; ANR) [ANR-13-BSV4-0011] and by the French Government through the ‘Investments for the Future’ LABEX SIGNALIFE [ANR-11-LABX-0028-01] to M.S., by the Spanish Government (BFU2007-60263 and BFU2010-17305) to A.F, and by the Medical Research Council (MR/K013750/1) to T.T. N.R.-R. is funded by a postdoctoral fellowship from the Ville de Nice, France (“Aide Individuelle aux Jeunes Chercheurs 2016”).Peer reviewe

Cajal and Lorente de Nó on cortical interneurons: Coincidences and progress

This essay explores the contributions to the organization of neuronal microcircuits in the cerebral cortex by Rafael Lorente de Nó, a renowned disciple of Santiago Ramón y Cajal. Lorente de Nó was impressed by the advances in functional parcellation of the cerebral cortex, and wished to find an anatomical correlate, not in cytoarchitectonic charts but in the fine details of neurons and (soon) of neuronal circuits within a cortical locale. His early analysis culminated in two major papers in 1933 and 1934: he introduced a hypothetical frame in which to integrate circuit anatomical complexity with the ideas on the physiology of the neuron prevalent at the time. In an interlude (1934–1938), Lorente embarked in studies of neuron physiology that inclined him to a reductionist interpretation of the axon as the main functionally relevant entity of neurons. This essay describes my attempts at tracing the links between the master's tradition, the minutiae in the early Golgi studies by Lorente and his concepts of neurophysiology. These are the bases to approach his final synthesis: The cerebral cortex: architecture, intracortical connections and motor projections, published as an invited chapter in J.F. Fulton's Physiology of the Nervous System in 1938.Supported by Ministerio de Educación y Ciencia Grant BFU2004-04660.Peer reviewe