The organization of the transcriptional network in specific neuronal classes

Kellen D. Winden, Michael C. Oldham, Karoly Mirnics, Philip J. Ebert, Christo H. Swan, Pat Levitt, John L. Rubenstein, Steve Horvath, Daniel H. Geschwind

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Genome-wide expression profiling has aided the understanding of the molecular basis of neuronal diversity, but achieving broad functional insight remains a considerable challenge. Here, we perform the first systems-level analysis of microarray data from single neuronal populations using weighted gene co-expression network analysis to examine how neuronal transcriptome organization relates to neuronal function and diversity. We systematically validate network predictions using published proteomic and genomic data. Several network modules of co-expressed genes correspond to interneuron development programs, in which the hub genes are known to be critical for interneuron specification. Other co-expression modules relate to fundamental cellular functions, such as energy production, firing rate, trafficking, and synapses, suggesting that fundamental aspects of neuronal diversity are produced by quantitative variation in basic metabolic processes. We identify two transcriptionally distinct mitochondrial modules and demonstrate that one corresponds to mitochondria enriched in neuronal processes and synapses, whereas the other represents a population restricted to the soma. Finally, we show that galectin-1 is a new interneuron marker, and we validate network predictions in vivo using Rgs4 and Dlx1/2 knockout mice. These analyses provide a basis for understanding how specific aspects of neuronal phenotypic diversity are organized at the transcriptional level.

Original languageEnglish
Article number291
JournalMolecular systems biology
Volume5
DOIs
Publication statusPublished - Jan 20 2009

Keywords

  • Development
  • Microarray
  • Mitochondria
  • Neuronal diversity
  • Systems biology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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  • Cite this

    Winden, K. D., Oldham, M. C., Mirnics, K., Ebert, P. J., Swan, C. H., Levitt, P., Rubenstein, J. L., Horvath, S., & Geschwind, D. H. (2009). The organization of the transcriptional network in specific neuronal classes. Molecular systems biology, 5, [291]. https://doi.org/10.1038/msb.2009.46