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The Requirement of Nkx2-1 in the Temporal Specification of Cortical Interneuron Subtypes
Open accessAbstract
Previous work has demonstrated that the character of mouse cortical interneuron subtypes can be directly related to their embryonic temporal and spatial origins. The relationship between embryonic origin and the character of mature interneurons is likely reflected by the developmental expression of genes that direct cell fate. However, a thorough understanding of the early genetic events that specify subtype identity has been hampered by the perinatal lethality resulting from the loss of genes implicated in the determination of cortical interneurons. Here, we employ a conditional loss-of-function approach to demonstrate that the transcription factor Nkx2-1 is required for the proper specification of specific interneuron subtypes. Removal of this gene at distinct neurogenic time points results in a switch in the subtypes of neurons observed at more mature ages. Our strategy reveals a causal link between the embryonic genetic specification by Nkx2-1 in progenitors and the functional attributes of their neuronal progeny in the mature nervous system.
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“MGE/POA progenitor cells take on properties of the LGE and CGE in mice lacking Nkx2-1”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Butt et al., 2008
In the citing paper
“MGE progenitors preferentially express the transcription factor Nkx2.1 (147, 148, 829, 1233), which must be downregulated in migrating postmitotic cells in order for them to avoid the striatum and reach the cortex”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [148]
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Metadata
- Authors
- Butt, S. J. B., Sousa, V. H., Fuccillo, M. V., Hjerling-Leffler, J., Miyoshi, G., Kimura, S., & Fishell, G.
- Affiliations
- New York University (US)
- National Institutes of Health (US)
- Corresponding author
- Fishell, Gord
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 59
- Issue
- 5
- Pages
- 722-732
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2562525
- OpenAlex
- W2032232458
- Cited by
- 330
- References
- 58
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 11 · 2023: 21 · 2022: 14 · 2021: 16 · 2020: 16 · 2019: 21 · 2018: 23 · 2017: 15 · 2016: 18 · 2015: 13 · 2014: 24 · 2013: 27 · 2012: 15
- FWCI
- 8.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1780 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH068469, R01MH071679, R37MH071679)
- Fogarty International Center
- National Institute of Neurological Disorders and Stroke (R01NS032993, R01NS039007)
- 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
- TTF-1, temporal specifications, conditional knockout, neurogenesis, neuronal precursors, transcription factors, perinatal lethality, mouse brain development
- MeSH terms
- Thyroid Nuclear Factor 1, Age Factors, Animals, Animals, Newborn, beta-Galactosidase, Cell Differentiation, Cerebral Cortex, Electroencephalography, Embryo, Mammalian, Estrogen Antagonists, Female, Interneurons, Male, Mice, Transgenic, Mutation, Nerve Tissue Proteins, Nuclear Proteins, Seizures, Stem Cells, Tamoxifen, Transcription Factors, Gene Expression Regulation, Developmental, Body Patterning, Green Fluorescent Proteins, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins
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