Dlx1&2-Dependent Expression of Zfhx1b (Sip1, Zeb2) Regulates the Fate Switch between Cortical and Striatal Interneurons
Open accessAbstract
Mammalian pallial (cortical and hippocampal) and striatal interneurons are both generated in the embryonic subpallium, including the medial ganglionic eminence (MGE). Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE, directly downstream of Dlx1&2, to generate cortical interneurons that express Cxcr7, MafB, and cMaf. In its absence, Nkx2-1 expression is not repressed, and cells that ordinarily would become cortical interneurons appear to transform toward a subtype of GABAergic striatal interneurons. These results show that Zfhx1b is required to generate cortical interneurons, and suggest a mechanism for the epilepsy observed in humans with Zfhx1b mutations (Mowat-Wilson syndrome).
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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 McKinsey et al., 2013
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- Authors
- McKinsey, G. L., Lindtner, S., Trzcinski, B., Visel, A., Pennacchio, L. A., Huylebroeck, D., Higashi, Y., & Rubenstein, J. L. R.
- Affiliations
- University of California, San Francisco (US)
- University of Michigan (US)
- Lawrence Berkeley National Laboratory (US)
- KU Leuven (BE)
- Aichi Human Service Center (JP)
- Corresponding author
- Rubenstein, John L.R.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 77
- Issue
- 1
- Pages
- 83-98
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3547499
- OpenAlex
- W2000966516
- Cited by
- 153
- References
- 64
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 13 · 2020: 14 · 2019: 12 · 2018: 11 · 2017: 16 · 2016: 14 · 2015: 14 · 2014: 15 · 2013: 13
- FWCI
- 6.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Lirias (submittedVersion)
- Funders
- National Institute of Mental Health (R37MH049428, R01MH081880)
- National Human Genome Research Institute (R01HG003988)
- National Institute of General Medical Sciences (T32GM007449)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063720)
- National Institute of Neurological Disorders and Stroke (R01NS062859, R01 NS062859A)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- ZEB2, DLX1, Dlx2, cortical interneurons, striatal interneurons, medial ganglionic eminence, subpallium, TTF-1, MAFB, c-Maf, CXCR7, GABAergic interneurons, Mowat-Wilson syndrome, epilepsy, gene regulatory networks
- MeSH terms
- Zinc Finger E-box Binding Homeobox 2, Animals, Animals, Newborn, Base Sequence, Cells, Cultured, Cerebral Cortex, Corpus Striatum, Genes, Homeobox, Interneurons, Mice, Transgenic, Molecular Sequence Data, Repressor Proteins, Transcription Factors, Mice, Knockout, Homeodomain Proteins, Gene Expression Regulation, Developmental, Mice, Neurogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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