Single-cell transcriptomics of the early developing mouse cerebral cortex disentangle the spatial and temporal components of neuronal fate acquisition

Development. 2021 Jul 15;148(14):dev197962. doi: 10.1242/dev.197962. Epub 2021 Jul 16.

Abstract

In the developing cerebral cortex, how progenitors that seemingly display limited diversity end up producing a vast array of neurons remains a puzzling question. The prevailing model suggests that temporal maturation of progenitors is a key driver in the diversification of the neuronal output. However, temporal constraints are unlikely to account for all diversity, especially in the ventral and lateral pallium where neuronal types significantly differ from their dorsal neocortical counterparts born at the same time. In this study, we implemented single-cell RNAseq to sample the diversity of progenitors and neurons along the dorso-ventral axis of the early developing pallium. We first identified neuronal types, mapped them on the tissue and determined their origin through genetic tracing. We characterised progenitor diversity and disentangled the gene modules underlying temporal versus spatial regulations of neuronal specification. Finally, we reconstructed the developmental trajectories followed by ventral and dorsal pallial neurons to identify lineage-specific gene waves. Our data suggest a model by which discrete neuronal fate acquisition from a continuous gradient of progenitors results from the superimposition of spatial information and temporal maturation.

Keywords: Cerebral cortex; Fate acquisition; Neuronal diversity; Neuronal specification; Ventral pallium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Embryo, Mammalian
  • Female
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins
  • Neurogenesis / physiology
  • Neurons / metabolism*
  • Proto-Oncogene Proteins / metabolism
  • Transcriptome*

Substances

  • Forkhead Transcription Factors
  • Foxg1 protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • proto-oncogene protein Pbx3