Sequential Transcriptional Waves Direct the Differentiation of Newborn Neurons in the Mouse Neocortex

Science. 2016 Mar 25;351(6280):1443-6. doi: 10.1126/science.aad8361. Epub 2016 Mar 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cerebral Ventricles / cytology
  • Cerebral Ventricles / embryology
  • DNA-Binding Proteins / genetics
  • Female
  • GPI-Linked Proteins / genetics
  • Green Fluorescent Proteins / genetics
  • Male
  • Mice
  • Neocortex / cytology
  • Neocortex / embryology*
  • Nerve Tissue Proteins / genetics
  • Neural Stem Cells / cytology
  • Neurogenesis / genetics*
  • Neurons / cytology*
  • Neuropeptides / genetics
  • SOXB1 Transcription Factors / genetics
  • Transcription, Genetic*
  • Transcriptome

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • GPI-Linked Proteins
  • Nerve Tissue Proteins
  • Neurod2 protein, mouse
  • Neurog2 protein, mouse
  • Neuropeptides
  • Nrn1 protein, mouse
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Tbr1 protein, mouse
  • Green Fluorescent Proteins