Correlated gene expression and target specificity demonstrate excitatory projection neuron diversity
Abstract
The neocortex contains diverse populations of excitatory neurons segregated by layer and further definable by their specific cortical and subcortical projection targets. The current study describes a systematic approach to identify molecular correlates of specific projection neuron classes in mouse primary somatosensory cortex (S1), using a combination of in situ hybridization (ISH) data mining, marker gene colocalization, and combined retrograde labeling with ISH for layer-specific marker genes. First, we identified a large set of genes with specificity for each cortical layer, and that display heterogeneous patterns within those layers. Using these genes as markers, we find extensive evidence for the covariation of gene expression and projection target specificity in layer 2/3, 5, and 6, with individual genes labeling neurons projecting to specific subsets of target structures. The combination of gene expression and target specificity imply a great diversity of projection neuron classes that is similar to or greater than that of GABAergic interneurons. The covariance of these 2 phenotypic modalities suggests that these classes are both discrete and genetically specified.
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Expression of specific layer 5b marker genes, especially Slc17a8, together with low methylation in aligned mL6-1 cells, confirmed the layer 5b assignment.
“However, the expression of several specific layer 5b marker genes, most notably Slc17a8 (Sorensen et al., 2015), and their corresponding low methylation pattern in the aligned cluster mL6–1 cells, enabled us to confirm this assignment (Figure S6A).”
From Single-Cell Multi-omic Integration Compares and Contrasts Features of Brain Cell Identity (2019) · cites this paper as Sorensen et al., 2015
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- Authors
- Sorensen, S. A., Bernard, A., Menon, V., Royall, J. J., Glattfelder, K. J., Desta, T., Hirokawa, K., Mortrud, M., Miller, J. A., Zeng, H., Hohmann, J. G., Jones, A. R., & Lein, E. S.
- Affiliations
- Allen Institute for Brain Science (US)
- ORCID
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-09-07
- Volume
- 25
- Issue
- 2
- Pages
- 433-449
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2134437091
- Cited by
- 131
- References
- 44
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 14 · 2023: 6 · 2022: 9 · 2021: 16 · 2020: 8 · 2019: 13 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 7 · 2014: 11 · 2013: 2
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- neocortex, primary somatosensory cortex, cortical layers, retrograde tracing, neuronal heterogeneity, GABAergic interneurons, mice
- MeSH terms
- Animals, Atlases as Topic, Male, Mice, Inbred C57BL, Neural Pathways, Neurons, Somatosensory Cortex, Gene Expression, In Situ Hybridization, Fluorescence, Mice, Neuronal Tract-Tracers, Data Mining
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