Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutants
Open accessAbstract
Mice lacking the Dlx1 and Dlx2 homeobox genes (Dlx1/2 mutants) have severe deficits in subpallial differentiation, including overexpression of the Gsx1 and Gsx2 homeobox genes. To investigate whether Gsx overexpression contributes to the Dlx1/2 mutant phenotypes, we made compound loss-of-function mutants. Eliminating Gsx2 function from the Dlx1/2 mutants rescued the increased expression of Ascl1 and Hes5 (Notch signaling mediators) and Olig2 (oligodendrogenesis mediator). In addition, Dlx1/2;Gsx2 mutants, like Dlx1/2;Ascl1 mutants, exacerbated the Gsx2 and Dlx1/2 patterning and differentiation phenotypes, particularly in the lateral ganglionic eminence (LGE) caudal ganglionic eminence (CGE), and septum, including loss of GAD1 expression. On the other hand, eliminating Gsx1 function from the Dlx1/2 mutants (Dlx1/2;Gsx1 mutants) did not severely exacerbate their phenotype; on the contrary, it resulted in a partial rescue of medial ganglionic eminence (MGE) properties, including interneuron migration to the cortex. Thus, despite their redundant properties, Gsx1 and -2 have distinct interactions with Dlx1 and -2. Gsx2 interaction is strongest in the LGE, CGE, and septum, whereas the Gsx1 interaction is strongest in the MGE. From these studies, and earlier studies, we present a model of the transcriptional network that regulates early steps of subcortical development.
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A regulatory network of Dlx1, Dlx2, Ascl1, Gsx1, and Gsx2 is required for specification of all GABAergic neurons in the subpallium.
“A regulatory network of genes encoding the transcription factors Dlx1, Dlx2, Ascl1, Gsx1 and Gsx2 is required for the specification of all GABAergic neurons in the subpallium”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Wang et al., 2013
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Additional file 4 of Prenatal alcohol exposure is a leading cause of interneuronopathy in humans
Marguet, F., Friocourt, G., Brosolo, M., Sauvestre, F., Marcorelles, P., Lesueur, C., Marret, S., Gonzalez, B. J., & Laquerrière, A. (2020) · Figshare · doi:10.6084/m9.figshare.13310404
Additional file 2 of Prenatal alcohol exposure is a leading cause of interneuronopathy in humans
Marguet, F., Friocourt, G., Brosolo, M., Sauvestre, F., Marcorelles, P., Lesueur, C., Marret, S., Gonzalez, B. J., & Laquerrière, A. (2020) · Figshare · doi:10.6084/m9.figshare.13310392
Additional file 3 of Prenatal alcohol exposure is a leading cause of interneuronopathy in humans
Marguet, F., Friocourt, G., Brosolo, M., Sauvestre, F., Marcorelles, P., Lesueur, C., Marret, S., Gonzalez, B. J., & Laquerrière, A. (2020) · Figshare · doi:10.6084/m9.figshare.13310398
Additional file 1 of Prenatal alcohol exposure is a leading cause of interneuronopathy in humans
Marguet, F., Friocourt, G., Brosolo, M., Sauvestre, F., Marcorelles, P., Lesueur, C., Marret, S., Gonzalez, B. J., & Laquerrière, A. (2020) · Figshare · doi:10.6084/m9.figshare.13310389
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Dlx1&2 directly promote expression of Cxcl14 to control synapse development and interneuron survival
Guo, T., Lindtner, S., Hu, J. S., Darbandi, S. F., Wang, Y., Pai, E. L.-L., Ypsilanti, A. R., van Velthoven, C. T. J., Nord, A. S., & Rubenstein, J. L. R. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2616055123
- Authors
- Wang, B., Long, J. E., Flandin, P., Pla, R., Waclaw, R. R., Campbell, K., & Rubenstein, J. L. R.
- Affiliations
- University of California, San Francisco (US)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Rubenstein, John L.R.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2013-03-18
- Volume
- 521
- Issue
- 7
- Pages
- 1561-1584
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- PMC
- PMC3615175
- OpenAlex
- W2008992192
- Cited by
- 85
- References
- 40
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 12 · 2021: 7 · 2020: 12 · 2019: 7 · 2018: 5 · 2017: 8 · 2016: 1 · 2015: 6 · 2014: 4 · 2013: 5
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Update notices
- erratum (2024-02-16)
- Open access
- bronze
- doi.org
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Larry L. Hillblom Foundation
- National Alliance for Research on Schizophrenia and Depression
- Weston Havens Foundation
- Ministerio de Economía y Competitividad
- National Institute of Mental Health (MH049428, MH081880, R37MH049428, R01MH081880)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063720)
- National Institute of Neurological Disorders and Stroke (R01NS044080)
- 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
- Gsx2, DLX1, Dlx2, lateral ganglionic eminence, caudal ganglionic eminence, medial ganglionic eminence, septum, interneuron migration, ASCL1, Hes5, Olig2, Notch signaling, transcriptional regulatory networks, GAD1
- MeSH terms
- Animals, Brain, Embryo, Mammalian, Fluorescent Antibody Technique, Mice, Mutant Strains, Phenotype, Transcription Factors, In Situ Hybridization, Homeodomain Proteins, Mice, Neurogenesis
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