Gli3 Is Required for Maintenance and Fate Specification of Cortical Progenitors
Open accessAbstract
Gli3, one of three vertebrate Gli transcription factors in Hedgehog (Hh) pathway, is processed into a repressor form (Gli3R) in the absence of Hh signal and acts as the major negative transducer of the pathway. Although the role of Gli3 in embryonic patterning has been extensively studied, its role in cortical neurogenesis, especially in the regulation of neural progenitors in proliferation and cell fate specification, is largely unknown. To bypass the patterning defects caused by loss of Gli3, we conditionally deleted Gli3 after patterning was complete in mouse. Our results from birthdating and in utero electroporation experiments demonstrate that the Gli3, specifically Gli3R, is critical for specifying the fate of cortical neurons that are generated following a stereotypical temporal order. Moreover,Gli3 is required for maintaining the cortical progenitors in active cell cycle, suggesting that cells may acquire differentiated status as they turn off Gli3 expression during neurogenesis.
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Both genes are known regulators of mouse cortical development and are associated with developmental disorders in humans.
“Both genes are known regulators of mouse cortical development33–35 and are associated with developmental disorders in humans14,36.”
From Inferring and perturbing cell fate regulomes in human brain organoids (2023) · cites this paper as [34]
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Cites
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237 · see citing works
The Glial Nature of Embryonic and Adult Neural Stem Cells
Kriegstein, A., & Alvarez-Buylla, A. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135600 · Cited by 2,475 · see citing works
Noctor, S. C., Martínez-Cerdeño, V., Ivic, L., & Kriegstein, A. R. (2004) · Nature Neuroscience · doi:10.1038/nn1172 · Cited by 2,229 · see citing works
The cell biology of neurogenesis
Götz, M., & Huttner, W. B. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1739 · Cited by 2,130 · see citing works
Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P. C., Bock, R., Klein, R., & Schütz, G. (1999) · Nature Genetics · doi:10.1038/12703 · Cited by 1,841 · see citing works
Neuronal subtype specification in the cerebral cortex
Molyneaux, B. J., Arlotta, P., Menezes, J. R. L., & Macklis, J. D. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2151 · Cited by 1,632 · see citing works
Regulation of Cerebral Cortical Size by Control of Cell Cycle Exit in Neural Precursors
Chenn, A., & Walsh, C. A. (2002) · Science · doi:10.1126/science.1074192 · Cited by 1,431 · see citing works
Control of Neuronal Precursor Proliferation in the Cerebellum by Sonic Hedgehog
Wechsler‐Reya, R. J., & Scott, M. P. (1999) · Neuron · doi:10.1016/s0896-6273(00)80682-0 · Cited by 1,343 · see citing works
Englund, C., Fink, A., Lau, C., Pham, D., Daza, R. A. M., Bulfone, A., Kowalczyk, T., & Hevner, R. F. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2899-04.2005 · Cited by 1,261 · see citing works
Wang, B., Fallon, J. F., & Beachy, P. A. (2000) · Cell · doi:10.1016/s0092-8674(00)80678-9 · Cited by 1,014 · see citing works
Hui, C., & Joyner, A. L. (1993) · Nature Genetics · doi:10.1038/ng0393-241 · Cited by 707 · see citing works
In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog
Ahn, S., & Joyner, A. L. (2005) · Nature · doi:10.1038/nature03994 · Cited by 699 · see citing works
Self-citationNeuronal position in the developing brain is regulated by mouse disabled-1
Howell, B. W., Hawkes, R., Soriano, P., & Cooper, J. A. (1997) · Nature · doi:10.1038/39607 · Cited by 692 · see citing works
A mitogen gradient of dorsal midline Wnts organizes growth in the CNS
Megason, S. G., & McMahon, A. P. (2002) · Development · doi:10.1242/dev.129.9.2087 · Cited by 681 · see citing works
The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall
Takahashi, T., Nowakowski, R. S., & Caviness, V. S. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-09-06046.1995 · Cited by 673 · see citing works
Hui, C., Slusarski, D. C., Platt, K. A., Holmgren, R. A., & Joyner, A. L. (1994) · Developmental Biology · doi:10.1006/dbio.1994.1097 · Cited by 480 · see citing works
The genetics of early telencephalon patterning: some assembly required
Hébert, J. M., & Fishell, G. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2463 · Cited by 377 · see citing works
Sessa, A., Mao, C., Hadjantonakis, A., Klein, W. H., & Broccoli, V. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.028 · Cited by 372 · see citing works
Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development
Fuccillo, M., Joyner, A., & Fishell, G. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1990 · Cited by 349 · see citing works
Gal, J. S., Morozov, Y. M., Ayoub, A. E., Chatterjee, M., RAKIC, P. T., & Haydar, T. F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4499-05.2006 · Cited by 343 · see citing works
Rallu, M., Machold, R., Gaiano, N., Corbin, J. G., McMahon, A. P., & Fishell, G. (2002) · Development · doi:10.1242/dev.129.21.4963 · Cited by 280 · see citing works
Palma, V., & Altaba, A. R. I. (2003) · Development · doi:10.1242/dev.00930 · Cited by 274 · see citing works
Cell cycle control of mammalian neural stem cells: putting a speed limit on G1
Salomoni, P., & Calegari, F. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.01.006 · Cited by 272 · see citing works
The Generation Of Neuronal Diversity In The Central Nervous System
McConnell, S. K. (1991) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.14.030191.001413 · Cited by 247 · see citing works
<i>Gli3</i>is required for<i>Emx</i>gene expression during dorsal telencephalon development
Theil, T., Alvarez-Bolado, G., Walter, A., & Rüther, U. (1999) · Development · doi:10.1242/dev.126.16.3561 · Cited by 228 · see citing works
Xu, Q., Guo, L., Moore, H., Waclaw, R. R., Campbell, K., & Anderson, S. A. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.004 · Cited by 218 · see citing works
Dorsoventral Patterning of the Telencephalon Is Disrupted in the Mouse Mutant extra-toesJ
Tole, S., Ragsdale, C. W., & Grove, E. A. (2000) · Developmental Biology · doi:10.1006/dbio.1999.9509 · Cited by 196 · see citing works
Hedgehog signaling is involved in development of the neocortex
Komada, M., Saitsu, H., Kinboshi, M., Miura, T., Shiota, K., & Ishibashi, M. (2008) · Development · doi:10.1242/dev.015891 · Cited by 195 · see citing works
Xu, Q., Wonders, C. P., & Anderson, S. A. (2005) · Development · doi:10.1242/dev.02090 · Cited by 184 · see citing works
Schimmang, T., Lemaistre, M., Vortkamp, A., & Rüther, U. (1992) · Development · doi:10.1242/dev.116.3.799 · Cited by 165 · see citing works
Genes and signaling events that establish regional patterning of the mammalian forebrain
Hoch, R. V., Rubenstein, J. L. R., & Pleasure, S. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.02.005 · Cited by 147 · see citing works
Blaess, S., Stephen, D. N., & Joyner, A. L. (2008) · Development · doi:10.1242/dev.015990 · Cited by 95 · see citing works
Fotaki, V., Yu, T. Y., Zaki, P. A., Mason, J. O., & Price, D. J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2673-06.2006 · Cited by 60 · see citing works
Lamination of the cerebral cortex is disturbed in Gli3 mutant mice
Friedrichs, M., Larralde, O., Skutella, T., & Theil, T. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.03.032 · Cited by 21 · see citing works
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Álvarez-Buylla, A., & Ihrie, R. A. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.05.008 · Cited by 100 · see citing works
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- Authors
- Wang, H., Ge, G., Uchida, Y., Luu, B., & Ahn, S.
- Affiliations
- National Institutes of Health (US)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
- Corresponding author
- Ahn, Sohyun
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-04-27
- Volume
- 31
- Issue
- 17
- Pages
- 6440-6448
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3096934
- OpenAlex
- W2106238824
- Cited by
- 93
- References
- 34
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 13 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 9 · 2019: 9 · 2018: 7 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 5 · 2012: 6
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (ZIAHD008781)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Gli3, Gli3 repressor, Hedgehog signaling, cortical progenitors, cortical neurogenesis, cell fate specification, conditional gene deletion, neural progenitor differentiation
- MeSH terms
- Zinc Finger Protein Gli3, Age Factors, Animals, Animals, Newborn, Bromodeoxyuridine, Cell Cycle, Cerebral Cortex, Embryo, Mammalian, Female, Intermediate Filament Proteins, Male, Mice, Transgenic, Models, Biological, Nerve Tissue Proteins, Nuclear Proteins, Proteins, Repressor Proteins, Homeodomain Proteins, Gene Expression Regulation, Developmental, Ki-67 Antigen, Body Patterning, In Situ Nick-End Labeling, RNA, Untranslated, Tumor Suppressor Proteins, Cell Proliferation, Green Fluorescent Proteins, Mice, Kruppel-Like Transcription Factors, Electrochemotherapy, Neural Stem Cells, Nestin
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