title: Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex.
abstract: During corticogenesis, excitatory neurons are born from progenitors located in the ventricular zone (VZ), from where they migrate to assemble into circuits. How neuronal identity is dynamically specified upon progenitor division is unknown. Here, we study this process using a high-temporal-resolution technology allowing fluorescent tagging of isochronic cohorts of newborn VZ cells. By combining this in vivo approach with single-cell transcriptomics in mice, we identify and functionally characterize neuron-specific primordial transcriptional programs as they dynamically unfold. Our results reveal early transcriptional waves that instruct the sequence and pace of neuronal differentiation events, guiding newborn neurons toward their final fate, and contribute to a road map for the reverse engineering of specific classes of cortical neurons from undifferentiated cells.
authors.affiliation: Department of Basic Neurosciences, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Telley
authors.affiliation: Department of Basic Neurosciences, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland.
authors.forename: Subashika
authors.initials: S
authors.lastname: Govindan
authors.affiliation: Department of Basic Neurosciences, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Prados
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stevant
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland.
authors.forename: Serge
authors.initials: S
authors.lastname: Nef
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Switzerland. Biomedical Research Foundation Academy of Athens, Greece. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Saudi Arabia. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Dermitzakis
authors.affiliation: Department of Basic Neurosciences, University of Geneva, Switzerland. Department of Psychiatry, Geneva University Hospital, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dayer
authors.affiliation: Department of Basic Neurosciences, University of Geneva, Switzerland. Clinic of Neurology, Geneva University Hospital, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. denis.jabaudon@unige.ch.
authors.forename: Denis
authors.initials: D
authors.lastname: Jabaudon
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D019579:Neocortex / Q000166:cytology / Q000196:embryology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology*; D009479:Neuropeptides / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D020825:T-Box Domain Proteins; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D058851:GPI-Linked Proteins; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D055748:SOXB1 Transcription Factors; D020825:T-Box Domain Proteins; C098995:Neurod2 protein, mouse; C102938:Neurog2 protein, mouse; C484377:Nrn1 protein, mouse; C527783:Sox2 protein, mouse; C492271:Tbr1 protein, mouse