The adverse outcome pathway (AOP) has been conceptualized in 2010 as an analytical construct to describe a sequential chain of causal links between key events, from a molecular initiating event leading to an adverse outcome (AO), considering several levels of biological organization. An AOP aims to identify and organize available knowledge about toxic effects of chemicals and drugs, either in ecotoxicology or toxicology, and it can be helpful in both basic and applied research and serve as a decision-making tool in support of regulatory risk assessment. The AOP concept has evolved since its introduction, and recent research in toxicology, based on integrative systems biology and artificial intelligence, gave it a new dimension.
View Article and Find Full Text PDFThe scientific knowledge produced by academic research can be valued in all sectors of human activity, including private sector. The ROVALTAIN Foundation organized a round-table during its scientific day in 2019. It crossed the points of view of academic scientists and industrial partners, addressing five main topics.
View Article and Find Full Text PDFThe orderly radial migration of cortical neurons from their birthplace in the germinal zones to their final destination in the cortical plate is a prerequisite for the functional assembly of microcircuits in the neocortex. Rodent and primate corticogenesis differ both quantitatively and qualitatively, particularly with respect to the generation of neurons of the supragranular layers. Marked area differences in the outer subventricular zone progenitor cell density impact the radial glia scaffold compactness which is likely to induce area differences in radial migration strategy.
View Article and Find Full Text PDFCurr Opin Neurobiol
February 2017
Neural stem cells go through a sequence of timely regulated gene expression and pattern of division mode to generate diverse neurons during brain development. During vertebrate cerebral cortex development, neural stem cells begin with proliferative symmetric divisions, subsequently undergo neurogenic asymmetric divisions, and finally gliogenic divisions. In this review, we explore the relationship between stem cell versus neural fate specification and the division mode.
View Article and Find Full Text PDFFront Cell Neurosci
February 2015
Recent data have uncovered that spindle size asymmetry (SSA) is a key component of asymmetric cell division (ACD) in the mouse cerebral cortex (Delaunay et al., 2014). In the present study we show that SSA is independent of spindle orientation and also occurs during cortical progenitor divisions in the ventricular zone (VZ) of the macaque cerebral cortex, pointing to a conserved mechanism in the mammalian lineage.
View Article and Find Full Text PDFThe regulation of asymmetric cell division (ACD) during corticogenesis is incompletely understood. We document that spindle-size asymmetry (SSA) between the two poles occurs during corticogenesis and parallels ACD. SSA appears at metaphase and is maintained throughout division, and we show it is necessary for proper neurogenesis.
View Article and Find Full Text PDFGenetic labeling based on the Cre/lox reporter system has allowed the creation of fate maps for progenitor cells and their offspring. In the diencephalon, pools of progenitors express the plp transcripts in the zona limitans intrathalamica (ZLI), the basal plate of the diencephalon (bpD), and the posterior part of the hypothalamus. We used plp-Cre transgenics crossed with either Rosa26-lox-lacZ (R26R) or actin-lox gfp (Z/EG) reporter mice to investigate the progeny of plp-expressing ventricular cells in the diencephalon.
View Article and Find Full Text PDFThe question of how neurons and glial cells are generated during the development of the CNS has over time led to two alternative models: either neuroepithelial cells are capable of giving rise to neurons first and to glial cells at a later stage (switching model), or they are intrinsically committed to generate one or the other (segregating model). Using the developing diencephalon as a model and by selecting a subpopulation of ventricular cells, we analyzed both in vitro, using clonal analysis, and in vivo, using inducible Cre/loxP fate mapping, the fate of neuroepithelial and radial glial cells generated at different time points during embryonic development. We found that, during neurogenic periods [embryonic day 9.
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