Lhx6 and Lhx8 Coordinately Induce Neuronal Expression of Shh that Controls the Generation of Interneuron Progenitors
Open accessAbstract
Lhx6 and Lhx8 transcription factor coexpression in early-born MGE neurons is required to induce neuronal Shh expression. We provide evidence that these transcription factors regulate expression of a Shh enhancer in MGE neurons. Lhx6 and Lhx8 are also required to prevent Nkx2-1 expression in a subset of pallial interneurons. Shh function in early-born MGE neurons was determined by genetically eliminating Shh expression in the MGE mantle zone (MZ). This mutant had reduced SHH signaling in the overlying progenitor zone, which led to reduced Lhx6, Lhx8, and Nkx2-1 expression in the rostrodorsal MGE and a preferential reduction of late-born somatostatin(+) and parvalbumin(+) cortical interneurons. Thus, Lhx6 and Lhx8 regulate MGE development through autonomous and nonautonomous mechanisms, the latter by promoting Shh expression in MGE neurons, which in turn feeds forward to promote the developmental program of the rostrodorsal MGE.
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Lhx6 and Lhx8 are co-expressed in some CNU and hypothalamus GABAergic types, but Lhx6 is also specifically expressed in MGE types.
“Lhx6 and Lhx8 are co-expressed in some CNU and hypothalamus GABAergic types110,111, but Lhx6 is also specifically expressed in MGE types.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [110]
The Results section reports Lhx6 and Lhx8 coexpression in more than 90% of cells in the embryonic MGE subventricular zone (page unavailable). The Discussion links both genes to striatal interneuron development, but our copy does not establish their coexpression in the cited CNU GABAergic types or address hypothalamic GABAergic types. (LLM, conf=0.84)
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- Authors
- Flandin, P., Zhao, Y., Vogt, D., Jeong, J., Long, J., Potter, G., Westphal, H., & Rubenstein, J. L. R.
- Affiliations
- University of California, San Francisco (US)
- National Institutes of Health (US)
- Corresponding author
- Rubenstein, John L.R.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 70
- Issue
- 5
- Pages
- 939-950
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3153409
- OpenAlex
- W2140101119
- Cited by
- 155
- References
- 42
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 11 · 2023: 11 · 2022: 9 · 2021: 9 · 2020: 9 · 2019: 6 · 2018: 8 · 2017: 11 · 2016: 10 · 2015: 20 · 2014: 13 · 2013: 13 · 2012: 8
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- State Tobacco Monopoly Administration
- National Institutes of Health
- National Institute of Mental Health (R37MH049428, R01MH081880)
- National Institute of Dental and Craniofacial Research (K99DE019486)
- 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 › Hedgehog Signaling Pathway Studies
- Keywords
- Lhx6, Lhx8, Sonic hedgehog, medial ganglionic eminence, TTF-1, somatostatin interneurons, parvalbumin interneurons, transcription factors, Sonic hedgehog signaling
- MeSH terms
- Thyroid Nuclear Factor 1, Age Factors, Animals, Animals, Newborn, Cell Differentiation, Cell Survival, Cells, Cultured, Embryo, Mammalian, Geniculate Bodies, Interneurons, Mice, Transgenic, Mutation, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Transcription Factors, Homeodomain Proteins, Gene Expression Regulation, Developmental, Electrophoretic Mobility Shift Assay, Cell Proliferation, Mice, Hedgehog Proteins, Neural Stem Cells, LIM-Homeodomain Proteins
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