Spatial genetic patterning of the embryonic neuroepithelium generates GABAergic interneuron diversity in the adult cortex
Open accessAbstract
Cortical pyramidal cells are generated from pallial neuroepithelial precursors, whereas GABAergic interneurons originate in subpallial germinal zones and migrate tangentially to reach the cortex. Using Cre-lox technology in transgenic mice and a series of molecular markers that subdivide the subpallial neuroepithelium into small domains, we fate-map precursor pools and identify interneurons generated from each domain. Cortical interneurons expressing calbindin, parvalbumin, and somatostatin are generated exclusively from Lhx6 (Lim homeobox 6)-expressing precursors in the medial ganglionic eminence (MGE). Martinotti cells that coexpress calretinin and somatostatin are generated from the dorsal region of the MGE neuroepithelium that expresses Nkx6.2 (NK2 transcription factor-related 6.2). Most neuropeptide Y-expressing cells and all bipolar calretinin-expressing interneurons are generated outside the MGE, from the germinal zones of the lateral/caudal ganglionic eminences that express Gsh2 (genomic screened homeobox 2). Our data demonstrate that subpallial neuroepithelial domains defined by expression of genetic determinants generate distinct interneuron subtypes, thereby contributing to the generation of cortical interneuron heterogeneity observed in the adult cortex.
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The dorsal MGE has a strong bias toward generating SST+ interneurons, whereas ventrocaudal domains produce a larger fraction of PV+ neurons.
“the dorsal MGE has a strong bias toward the generation of SST+ interneurons, whereas the ventrocaudal domains produce a larger fraction of PV+ neurons”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Fogarty et al., 2007
Each progenitor domain in the MGE generates multiple types of cortical interneurons.
“Each progenitor domain in the MGE generates multiple types of cortical interneurons”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Fogarty et al., 2007
The Nkx2.1 lineage also gives rise to dendrite targeting somatostatin (SST)-expressing interneurons, and thus use of Nkx2.1-Cre lines in isolation results in recombination within a wide variety of perisomatic and dendrite targeting interneurons.
“However, the Nkx2.1 lineage also gives rise to dendrite targeting somatostatin (SST)-expressing interneurons, and thus use of Nkx2.1-Cre lines in isolation will result in recombination within a wide variety of perisomatic and dendrite targeting interneurons (147, 339, 1138, 1233, 1235).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [339]
Further divergence in O-LM and Martinotti cell molecular profiles is evidenced by the frequent coexpression of CR with SST in Martinotti cells, a molecular signature that is absent from the hippocampus.
“Further divergence in O-LM and Martinotti cell molecular profiles is evidenced by the frequent coexpression of CR with SST in Martinotti cells, a molecular signature that is absent from the hippocampus (203, 339, 1042, 1238).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [339]
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References 60 · Cited by 412
- Authors
- Fogarty, M., Grist, M., Gelman, D., Marín, O., Pachnis, V., & Kessaris, N.
- Affiliations
- University College London (GB)
- Instituto de Neurociencias (ES)
- National Institute for Medical Research (GB)
- Corresponding author
- Kessaris, Nicoletta
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-10-10
- Volume
- 27
- Issue
- 41
- Pages
- 10935-10946
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672847
- OpenAlex
- W2007648520
- Cited by
- 412
- References
- 60
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 14 · 2023: 19 · 2022: 20 · 2021: 14 · 2020: 17 · 2019: 18 · 2018: 29 · 2017: 26 · 2016: 27 · 2015: 21 · 2014: 30 · 2013: 31 · 2012: 17
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- University College London
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- GABAergic interneurons, medial ganglionic eminence, lateral ganglionic eminence, caudal ganglionic eminence, Lhx6, NKX6-2, GSH2, calbindin, parvalbumin, somatostatin, calretinin, neuropeptide Y, Martinotti cells, fate mapping, interneuron migration
- MeSH terms
- Age Factors, Animals, Cerebral Cortex, gamma-Aminobutyric Acid, Interneurons, Mice, Transgenic, Neuroepithelial Cells, Mice
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