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Cellular and Genetic Mechanisms of Progenitor Fate Plasticity in the Neocortex

English title Cellular and Genetic Mechanisms of Progenitor Fate Plasticity in the Neocortex
Applicant Jabaudon Denis
Number 179423
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.08.2018 - 31.07.2022
Approved amount 1'224'000.00
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Keywords (3)

cortical circuits; neuronal identity; cortical development

Lay Summary (French)

Lead
Comprendre et explorer la plasticité des progéniteurs neuronaux
Lay summary
Les différents types de neurones du cortex cérébral sont séquentiellement générés à partir de progéniteurs au cours du développement embryonnaire. On commence à comprendre les programmes génétiques qui sous-tendent cette progression, mais l'on n'est pas encore en mesure de manipuler ces programmes de manière coordonnée pour diriger le type de neurones produits. Dans le cadre de ce projet, nous explorerons la plasticité des progéniteurs du cortex cérébral dans le but de générer des types de neurones sur mesure à visée de médecine régénérative.
Direct link to Lay Summary Last update: 01.05.2018

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
157846 Self-Organizing Properties of Neocortical Circuits 01.04.2015 Temporary Backup Schemes

Abstract

During neocortical development, progenitors located in the ventricular zone (VZ) sequentially generate distinct subtypes of excitatory neurons which assemble to form the circuits for high-order sensory-motor and cognitive functions. Deep-layer, subcortically-projecting neurons are born first (on embryonic day (E) 12.5 in the mouse), while superficial-layer, intracortically-projecting neurons, are born later on, toward the end of corticogenesis (E15.5).While the programs controlling the progression from deep-layer neuron generation to superficial-layer generation normally unfold sequentially, they are also plastic since progenitor competence can be experimentally respecified through genetic and other experimental manipulations. Using state-of-the art transcriptomic approaches, here we propose to characterize the plasticity of neurogenic progenitors in the developing neocortex, and the transcriptional mechanisms that underlie it. Beyond their importance in understanding the molecular mechanisms controlling the generation of neuronal diversity, the experiments proposed here are directly relevant to optimize and refine regenerative medicine strategies, and to assess the potential of transplantation approaches for neurological disorders.
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