An intrinsic mechanism of corticogenesis from embryonic stem cells

• Published in: Nature Vol. 455; no. 7211; pp. 351 - 357
• Main Authors: Passante, Lara, Espuny-Camacho, Ira, Dimidschstein, Jordane, Herpoel, Adèle, Hourez, Raphael, Schiffmann, Serge N, Vanderhaeghen, Pierre, van den Ameele, Jelle, Gaillard, Afsaneh, Naeije, Gilles, Gaspard, Nicolas, Bouschet, Tristan
• Format: Journal Article Web Resource
• Language: English
• Published: London Nature Publishing Group UK 18.09.2008; Nature Publishing; Nature Publishing Group
• Subjects: Animal models in research; Animals; Axons - drug effects; Axons - physiology; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Biological and medical sciences; Cell Differentiation - drug effects; Cell Lineage - drug effects; Cerebral cortex; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - embryology; Development Biology; Development. Senescence. Regeneration. Transplantation; Embryology and Organogenesis; Embryonic stem cells; Embryonic Stem Cells - cytology; Embryonic Stem Cells - drug effects; Embryos; Fundamental and applied biological sciences. Psychology; Gene expression; Humanities and Social Sciences; Life Sciences; Methods; Mice; multidisciplinary; Neurobiology; Neurons; Neurons and Cognition; Neurosciences; Physiological aspects; Pyramidal Cells - drug effects; Science; Science (multidisciplinary); Sciences du vivant; Specifications; Stem cells; Veratrum Alkaloids - pharmacology; Vertebrates: nervous system and sense organs; Cerebral cortex; Embryo; Stem cell; Rodentia; Central nervous system; Projection; In vitro; Encephalon; Vertebrata; Mammalia; Treatment; Mouse; Animal; Light; Development; Graft; Pyramidal neuron; Subtype; Cellules souches embryonnaires; neurones corticaux; transplantation
• ISSN: 0028-0836; 1476-4687; 1476-4687; 1476-4679
• DOI: 10.1038/nature07287

The cerebral cortex develops through the coordinated generation of dozens of neuronal subtypes, but the mechanisms involved remain unclear. Here we show that mouse embryonic stem cells, cultured without any morphogen but in the presence of a sonic hedgehog inhibitor, recapitulate in vitro the major milestones of cortical development, leading to the sequential generation of a diverse repertoire of neurons that display most salient features of genuine cortical pyramidal neurons. When grafted into the cerebral cortex, these neurons develop patterns of axonal projections corresponding to a wide range of cortical layers, but also to highly specific cortical areas, in particular visual and limbic areas, thereby demonstrating that the identity of a cortical area can be specified without any influence from the brain. The discovery of intrinsic corticogenesis sheds new light on the mechanisms of neuronal specification, and opens new avenues for the modelling and treatment of brain diseases. A head start: cerebral cortex development The cerebral cortex is the most complex structure in the mammalian brain, containing many different neuronal cell subtypes. A study of mouse embryonic stem cells in cell culture now shows that the diverse repertoire of cortical neurons can be generated in vitro . In the absence of a morphogen and in the presence of a sonic hedgehog inhibitor, corticogenesis is an intrinsic property of mouse embryonic stem cells. This finding throws light on mechanisms of neuronal specification and suggests new avenues for the modelling and treatment of brain diseases.