Scientific Understanding of Consciousness
Cerebral Cortex Embryonic Development
Nature 455, 351-357 (18 September 2008)
An intrinsic mechanism of corticogenesis from embryonic stem cells
Nicolas Gaspard, Tristan Bouschet, Raphael Hourez, Jordane Dimidschstein, Gilles Naeije, Jelle van den Ameele, Ira Espuny-Camacho, Adèle Herpoel, Lara Passante, Serge N. Schiffmann, Afsaneh Gaillard3 & Pierre Vanderhaeghen
IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB)
Laboratory of Neurophysiology, Université Libre de Bruxelles (ULB), 808 Route de Lennik, B-1070 Brussels, Belgium
Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, Centre National de la Recherche Scientifique (CNRS), 40 avenue du recteur Pineau, Poitiers, F-86022, France
The cerebral cortex is the most complex structure in the mammalian brain, and displays an unparalleled diversity of neuronal subtypes. This complexity is established sequentially, starting with the emergence of the cortical primordium in the forebrain. Forebrain identity is thought to constitute a primitive pattern of neural identity, which is retained through the inhibition of caudalizing morphogen signals. The forebrain then undergoes patterning along the dorso–ventral axis, mainly through the induction of ventral identity by sonic hedgehog (SHH), secreted from the ventral neural tube and underlying tissue This leads to the specification of the two main populations of cortical neurons, pyramidal neurons and interneurons, which are generated from the dorsal and the ventral part of the telencephalon, respectively.
A next level of complexity emerges through the specification of different subtypes of cortical neurons that will populate specific cortical layers, where they exhibit specific patterns of gene expression and connectivity. This specification follows a coordinated temporal pattern: neurons from different layers are generated sequentially, but the underlying mechanisms remain poorly known. Finally, neurons from distinct cortical areas develop selective patterns of gene expression and projections, through the interplay between factors intrinsic to the cortex and extrinsic factors from the brain and body.
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Nature 455, 114-118 (4 September 2008)
Neurogenin 2 controls cortical neuron migration through regulation of Rnd2
Julian Ik-Tsen Heng, Laurent Nguyen, Diogo S. Castro, Céline Zimmer, Hendrik Wildner, Olivier Armant, Dorota Skowronska-Krawczyk, Francesco Bedogni, Jean-Marc Matter, Robert Hevner, François Guillemot
Division of Molecular Neurobiology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
Department of Biochemistry, Sciences II, University of Geneva, CH-1211 Geneva 4, Switzerland
Department of Pathology, University of Washington School of Medicine, Harborview Medical Center, Seattle, Washington 98104, USA
Motility is a universal property of newly generated neurons. Neurons migrate extensively after their birth to reach their permanent location in the nervous system. How cell migration is coordinately regulated with other aspects of neuron production is not well understood. Here we show that the proneural protein neurogenin 2 (Neurog2), which controls neurogenesis in the embryonic cerebral cortex, directly induces the expression of the small GTP-binding protein Rnd2 in newly generated mouse cortical neurons before they initiate migration. Our results identify Rnd2 as a novel essential regulator of neuronal migration in the cerebral cortex and demonstrate that Rnd2 is a major effector of Neurog2 function in the promotion of migration. Thus, a proneural protein controls the complex cellular behaviour of cell migration through a remarkably direct pathway involving the transcriptional activation of a small GTP-binding protein.
Rnd2 regulates cell morphology and cell movement and is an important component of the neurogenic program activated by Neurog2 in the cerebral cortex. In the embryonic telencephalon, Rnd2 is expressed at higher levels in dorsal than in ventral neurons, whereas the related gene Rnd3 is expressed in a complementary manner with higher expression ventrally. Thus, Rnd2 may be part of a program of neurogenesis that is specific to the dorsal telencephalon and confers unique properties to cortical neurons, whereas different Rnd proteins may participate in distinct programs of neurogenesis activated in other brain regions. Rnd proteins signal by multiple downstream pathways and may thus confer distinct migratory properties to different classes of newborn neurons.
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Science 8 July 1988: Vol. 241. no. 4862, pp. 170 - 176
Specification of cerebral cortical areas
Yale University School of Medicine, New Haven, CT 06510.
How the immense population of neurons that constitute the human cerebral neocortex is generated from progenitors lining the cerebral ventricle and then distributed to appropriate layers of distinctive cytoarchitectonic areas can be explained by the radial unit hypothesis. According to this hypothesis, the ependymal layer of the embryonic cerebral ventricle consists of proliferative units that provide a proto-map of prospective cytoarchitectonic areas. The output of the proliferative units is translated via glial guides to the expanding cortex in the form of ontogenetic columns, whose final number for each area can be modified through interaction with afferent input. Data obtained through various advanced neurobiological techniques, including electron microscopy, immunocytochemistry, [3H]thymidine and receptor autoradiography, retrovirus gene transfer, neural transplants, and surgical or genetic manipulation of cortical development, furnish new details about the kinetics of cell proliferation, their lineage relationships, and phenotypic expression that favor this hypothesis. The radial unit model provides a framework for understanding cerebral evolution, epigenetic regulation of the parcellation of cytoarchitectonic areas, and insight into the pathogenesis of certain cortical disorders in humans.
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