The organization of the transcriptional network in specific neuronal classes
Open accessAbstract
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.
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When evaluating co-expression across brain regions, hubs in modules associated with specific regions, such as the cerebellum, are usually markers for predominant cell types, such as granule cells.
“For example, when evaluating co-expression across brain regions, hubs in modules that are associated with specific regions, such as the cerebellum, are usually markers for predominant cell types, such as granule cells11,12,26,32.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [32]
The role of Tyrobp was experimentally validated in mice, showing that network structure is predictive, as previously demonstrated with co-expression networks.
“The role of Tyrobp was experimentally validated in mice170, showing that network structure is predictive, as had previously been demonstrated with co-expression networks32.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [32]
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- Authors
- Winden, K. D., Oldham, M. C., Mirnics, K., Ebert, P. J., Swan, C. H., Levitt, P., Rubenstein, J. L., Horvath, S., & Geschwind, D. H.
- Affiliations
- University of California, Los Angeles (US)
- Vanderbilt University (US)
- University of California, San Francisco (US)
- Corresponding author
- Geschwind, Daniel H
- ORCID
- Venue
- Molecular Systems Biology
- Published
- 2009-07-28
- Volume
- 5
- Issue
- 1
- Pages
- 291-291
- ISSN
- 1744-4292 (ISSN-L)
- PMC
- PMC2724976
- OpenAlex
- W2133863540
- Cited by
- 112
- References
- 85
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 11 · 2014: 13 · 2013: 13 · 2012: 6
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Systems Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- European Molecular Biology Organization
- National Institutes of Health
- National Institute of Mental Health (R37MH60233-06A1, R01 MH4942801, K05MH065670, R01MH049428, T32MH073526, R37MH060233)
- National Institute of General Medical Sciences (GM-08042, T32GM008042)
- National Institute of Neurological Disorders and Stroke (U24NS052108, U24 NS52108)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- neuronal heterogeneity, transcriptional regulatory networks, gene co-expression modules, interneuron specification, mitochondrial gene expression, galectin-1, RGS4, neuronal transcriptome, hub genes, synapses, neuronal energy metabolism
- MeSH terms
- Animals, Mitochondria, Neurons, Synapses, Gene Expression Profiling, Galectin 1, Mice, Gene Regulatory Networks
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