Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia

Anna Hoerder-Suabedissen*, Franziska M. Oeschger, Michelle Krishnan, T. Grant Belgard, Wei Zhi Wang, Sheena Lee, Caleb Webber, Enrico Petretto, A. David Edwards, Zoltan Molnar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)

Abstract

The subplate zone is a highly dynamic transient sector of the developing cerebral cortex that contains some of the earliest generated neurons and the first functional synapses of the cerebral cortex. Subplate cells have important functions in early establishment and maturation of thalamocortical connections, as well as in the development of inhibitory cortical circuits in sensory areas. So far no role has been identified for cells in the subplate in the mature brain and disease association of the subplate-specific genes has not been analyzed systematically. Here we present gene expression evidence for distinct roles of the mouse subplate across development as well as unique molecular markers to extend the repertoire of subplate labels. Performing systematic comparisons between different ages (embryonic days 15 and 18, postnatal day 8, and adult), we reveal the dynamic and constant features of the markers labeling subplate cells during embryonic and early postnatal development and in the adult. This can be visualized using the online database of subplate gene expression at https://molnar.dpag.ox.ac.uk/subplate/. We also identify embryonic similarities in gene expression between the ventricular zones, intermediate zone, and subplate, and distinct postnatal similarities between subplate, layer 5, and layers 2/3. The genes expressed in a subplate-specific manner at some point during development show a statistically significant enrichment for association with autism spectrum disorders and schizophrenia. Our report emphasizes the importance of the study of transient features of the developing brain to better understand neurodevelopmental disorders.

Original languageEnglish
Pages (from-to)3555-3560
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number9
DOIs
Publication statusPublished - 26 Feb 2013

Keywords

  • SPECTRUM DISORDERS
  • WHITE-MATTER
  • DEVELOPMENTAL HISTORY
  • Nxph4
  • SOMATOSENSORY CORTEX
  • interstitial white matter cells
  • THALAMOCORTICAL CONNECTIONS
  • DIFFERENTIATION
  • BRAIN
  • CORTICAL SUBPLATE
  • Tpd52l1
  • microarray
  • CEREBRAL-CORTEX
  • NEURONS
  • RNAseq

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