Optimization of interneuron function by direct coupling of cell migration and axonal targeting
Open accessAbstract
Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb-a gene that is preferentially expressed by these cells-cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex.
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GABAergic interneurons born in the ganglionic eminences migrate tangentially to the proper place within prefrontal subdomains.
“Born in the ganglionic eminences, GABAergic interneurons migrate tangentially to the proper place within the prefrontal subdomains [66, 67].”
From Development of prefrontal cortex (2022) · cites this paper as [66]
The Abstract says most cortical interneurons derive from the medial ganglionic eminence, and the Discussion says interneurons migrate tangentially to the developing cortex (page numbers unavailable). Neither passage establishes that they reach proper places within prefrontal subdomains; the paper discusses cortical migratory routes instead. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCortical interneurons are already fated to become Martinotti or non-Martinotti cells in the embryonic subpallium before entering the cortex, and the choice of migratory route is part of the intrinsic developmental program.
“This suggests that cortical interneurons are already fated to become Martinotti or non-Martinotti cells in the embryonic subpallium prior to entering the cortex, and that the choice of a particular migratory route is part of the intrinsic program controlling the development of interneurons.”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Lim et al., 2018
Specification of at least Martinotti and non-Martinotti SST+ interneuron types is independent of and prior to selection of a migratory route.
“which suggests that the specification of at least these two types of SST+ interneuron is independent of – and prior to – the selection of a migratory route”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Lim et al., 2018
SST+ Martinotti cells and SST+ non-Martinotti cells use different migratory routes to disperse through the cortex.
“SST+ Martinotti cells and SST+ non-Martinotti cells use different migratory routes to disperse through the cortex”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Lim et al., 2018
Experimentally reducing the number of SST+ neurons migrating through their normal route does not affect the ratio between Martinotti and non-Martinotti cells in the mature cortex, although it affects specific features of these cells.
“experimentally reducing the number of SST+ neurons migrating through their normal route does not affect the ratio between Martinotti and non-Martinotti cells in the mature cortex (although it affects specific features of these cells)”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Lim et al., 2018
Different types of interneuron use different migratory streams to reach the cortex.
“different types of interneuron use different migratory streams to reach the cortex”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Lim et al., 2018
SST+ Martinotti and PV+ translaminar interneurons preferentially migrate through the marginal zone, whereas non-Martinotti cells disperse through the subventricular zone.
“Recent work has added further support to this idea by showing that SST+ Martinotti and PV+ translaminar interneurons migrate preferentially through the MZ, while non-Martinotti cells disperse via the SVZ (Lim et al., 2018).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Lim et al., 2018
Migration of SST+ Martinotti cells through the marginal zone appears to belong to a broader developmental program that controls their layer 1 axonal arborization.
“Interestingly, the migration of SST+ Martinotti cells through the MZ seems to be part of a wider developmental program that controls the development of their axonal arborization in layer 1.”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Lim et al., 2018
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- Authors
- Lim, L., Pakan, J. M. P., Selten, M. M., Marques-Smith, A., Llorca, A., Bae, S. E., Rochefort, N. L., & Marín, O.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- German Center for Neurodegenerative Diseases (DE)
- King's College London (GB)
- Simons Initiative for the Developing Brain (GB)
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-06-18
- Volume
- 21
- Issue
- 7
- Pages
- 920-931
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6061935
- OpenAlex
- W2807977171
- Cited by
- 93
- References
- 67
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 10 · 2023: 13 · 2022: 11 · 2021: 15 · 2020: 18 · 2019: 9 · 2018: 4
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- DZNE Pub (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (102857/Z/13/Z)
- European Commission (631770, 624461)
- Simons Initiative for the Developing Brain
- Medical Research Council (MR/N026063/1)
- FP7 Ideas: European Research Council (293683)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Martinotti cells, somatostatin interneurons, interneuron migration, axon targeting, MAFB, cortical development, conditional gene deletion
- MeSH terms
- Animals, Axons, Cell Movement, Cerebral Cortex, Interneurons, Mice, Knockout, MafB Transcription Factor, GABAergic Neurons
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