Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex

Ludovic Telley; Subashika Govindan; Julien Prados; Isabelle Stevant; Serge Nef; Emmanouil Dermitzakis; Alexandre Dayer; Denis Jabaudon

doi:10.1126/science.aad8361

Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex

Ludovic Telley, Subashika Govindan, Julien Prados, Isabelle Stevant, Serge Nef, Emmanouil Dermitzakis, Alexandre Dayer, Denis Jabaudon

Research output: Contribution to journal › Article › peer-review

223 Scopus citations

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 neuronspecific 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.

Original language	English
Pages (from-to)	1443-1446
Number of pages	4
Journal	Science
Volume	351
Issue number	6280
DOIs	https://doi.org/10.1126/science.aad8361
State	Published - 25 Mar 2016
Externally published	Yes

Funding

ACKNOWLEDGMENTS: Annotated data are available at http://genebrowser.unige.ch/ science2016. We thank R. Hevner for the gift of the TBR1 antibody; A. Benoit, M. Lanzillo, and the Genomics Platform and FACS Facility of the University of Geneva for technical assistance; and E. Azim, A. Carleton, S. Tole, and the members of the Jabaudon laboratory for comments on the manuscript. Work in the Jabaudon laboratory is supported by the Swiss National Science Foundation (PP00P3-123447), the Synapsis Foundation, and the Brain and Behavior Foundation (NARSAD Grant). S.N. is funded by the Swiss SystemsX Interdisciplinary PhD Grant 51PHI0-141994. S.G. and I.S. are supported by the iGe3 PhD Award. A.D. is funded by the Swiss National Science Foundation and the National Center of Competence in Research (NCCR) Synapsy. The authors declare no competing interests. The supplementary materials contain additional data.

Funders	Funder number
Brain and Behavior Research Foundation
National Alliance for Research on Schizophrenia and Depression	51PHI0-141994
nccr – on the move
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	PP00P3-123447
Université de Genève
Stiftung Synapsis - Alzheimer Forschung Schweiz AFS

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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 neuronspecific 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.",

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AU - Dayer, Alexandre

AU - Jabaudon, Denis

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Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex

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