Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1
Open accessAbstract
GABAergic interneurons mainly originate in the medial ganglionic eminence (MGE) of the embryonic ventral telencephalon (VT) and migrate tangentially to the cortex, guided by membrane-bound and secreted factors. We found that Sip1 (Zfhx1b, Zeb2), a transcription factor enriched in migrating cortical interneurons, is required for their proper differentiation and correct guidance. The majority of Sip1 knockout interneurons fail to migrate to the neocortex and stall in the VT. RNA sequencing reveals that Sip1 knockout interneurons do not acquire a fully mature cortical interneuron identity and contain increased levels of the repulsive receptor Unc5b. Focal electroporation of Unc5b-encoding vectors in the MGE of wild-type brain slices disturbs migration to the neocortex, whereas reducing Unc5b levels in Sip1 knockout slices and brains rescues the migration defect. Our results reveal that Sip1, through tuning of Unc5b levels, is essential for cortical interneuron guidance.
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Repression of Nkx2-1 in cortical interneurons derived from the MGE requires Zfhx1b.
“Repression of Nkx2-1 in cortical interneurons derived from the MGE requires the function of the zinc-finger homeobox transcription factor Zfhx1b (McKinsey et al., 2013; van den Berghe et al., 2013).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as van den Berghe et al., 2013
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- Authors
- van den Berghe, V., Stappers, E., Vandesande, B., Dimidschstein, J., Kroes, R., Francis, A., Conidi, A., Lesage, F., Dries, R., Cazzola, S., Berx, G., Kessaris, N., Vanderhaeghen, P., van IJcken, W., Grosveld, F. G., Goossens, S., Haigh, J. J., Fishell, G., Goffinet, A., Aerts, S., Huylebroeck, D., & Seuntjens, E.
- Affiliations
- KU Leuven (BE)
- Université Libre de Bruxelles (BE)
- Vlaams Instituut voor Biotechnologie (BE)
- University College London (GB)
- Erasmus MC (NL)
- Ghent University (BE)
- NYU Langone Health (US)
- UCLouvain (BE)
- Corresponding author
- Huylebroeck, Danny
- Seuntjens, Eve
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 77
- Issue
- 1
- Pages
- 70-82
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2144628304
- Cited by
- 120
- References
- 62
- Citations by year
- 2025: 7 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 12 · 2020: 12 · 2019: 3 · 2018: 13 · 2017: 11 · 2016: 12 · 2015: 8 · 2014: 10 · 2013: 13
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Lirias (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Koninklijke Nederlandse Akademie van Wetenschappen
- Fonds De La Recherche Scientifique - FNRS
- Services Fédéraux des Affaires Scientifiques, Techniques et Culturelles
- 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
- ZEB2, cortical interneuron migration, medial ganglionic eminence, ventral telencephalon, UNC5B, GABAergic interneurons, neocortex, transcription factors, interneuron differentiation
- MeSH terms
- Netrin Receptors, Animals, Cell Movement, Cerebral Cortex, Interneurons, Mice, Transgenic, Nerve Tissue Proteins, Organ Culture Techniques, Receptors, Cell Surface, Telencephalon, Neocortex, Mice, Gene Knockout Techniques
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