Neuronal identity control by terminal selectors in worms, flies, and chordates
Abstract
How do post-mitotic neurons acquire and maintain their terminal identity? Genetic mutant analysis in the nematode Caenorhabditis elegans has revealed common molecular programs that control neuronal identity. Neuron type-specific combinations of transcription factors, called terminal selectors, act as master regulatory factors to initiate and maintain terminal identity programs through direct regulation of neuron type-specific effector genes. We will provide here an update on recent studies that solidify the terminal selector concept in worms, flies and chordates. We will also describe how the terminal selector concept has been expanded by recent work in C. elegans to explain neuronal subtype diversification and plasticity of neuronal identity.
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Transcription factors are considered key regulators of cell-type identity.
“Transcription factors are considered key regulators of cell-type identity88,89.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [89]
Cites
The structure of the nervous system of the nematode <i>Caenorhabditis elegans</i>
White, J. G., Southgate, E., Thomson, J. N., & Brenner, S. (1986) · Philosophical Transactions of the Royal Society of London. B, Biological Sciences · doi:10.1098/rstb.1986.0056 · Cited by 5,589 · see citing works
Comprehensive Genome-wide Protein-DNA Interactions Detected at Single-Nucleotide Resolution
Rhee, H. S., & Pugh, B. F. (2011) · Cell · doi:10.1016/j.cell.2011.11.013 · Cited by 760 · see citing works
A cellular and regulatory map of the cholinergic nervous system of C. elegans
Pereira, L., Kratsios, P., Serrano-Saiz, E., Sheftel, H., Mayo, A. E., Hall, D. H., White, J. G., LeBoeuf, B., Garcia, L. R., Alon, U., et al. (2015) · eLife · doi:10.7554/elife.12432 · Cited by 365 · see citing works
Self-citationModular Control of Glutamatergic Neuronal Identity in C. elegans by Distinct Homeodomain Proteins
Serrano‐Saiz, E., Poole, R. J., Felton, T., Zhang, F., Cruz, E. D. D. L., & Hobert, O. (2013) · Cell · doi:10.1016/j.cell.2013.09.052 · Cited by 271 · see citing works
Self-citationControl of type-D GABAergic neuron differentiation by C. elegans UNC-30 homeodomain protein
Jin, Y., Hoskins, R. A., & Horvitz, H. R. (1994) · Nature · doi:10.1038/372780a0 · Cited by 258 · see citing works
Ryan, K., Lu, Z., & Meinertzhagen, I. A. (2016) · eLife · doi:10.7554/elife.16962 · Cited by 244 · see citing works
Terminal Selectors of Neuronal Identity
Hobert, O. (2016) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2015.12.007 · Cited by 231 · see citing works
Self-citationPhenotypic convergence: distinct transcription factors regulate common terminal features
Konstantinides, N., Kapuralin, K., Fadil, C., Barboza, L., Satija, R., & Desplan, C. (2018) · Cell · doi:10.1016/j.cell.2018.05.021 · Cited by 226 · see citing works
Multi-Scale molecular deconstruction of the serotonin neuron system
Okaty, B. W., Freret, M. E., Rood, B. D., Brust, R. D., Hennessy, M. L., deBairos, D., Kim, J. C., Cook, M. N., & Dymecki, S. M. (2015) · Neuron · doi:10.1016/j.neuron.2015.10.007 · Cited by 217 · see citing works
Wang, S. S., Tsai, R. Y. L., & Reed, R. R. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-11-04149.1997 · Cited by 210 · see citing works
Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene
Kratsios, P., Stolfi, A., Levine, M., & Hobert, O. (2011) · Nature Neuroscience · doi:10.1038/nn.2989 · Cited by 181 · see citing works
Self-citationPet-1 is required across different stages of life to regulate serotonergic function
Liu, C., Maejima, T., Wyler, S. C., Casadesús, G., Herlitze, S., & Deneris, E. S. (2010) · Nature Neuroscience · doi:10.1038/nn.2623 · Cited by 178 · see citing works
Eastman, C., Horvitz, H. R., & Jin, Y. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-15-06225.1999 · Cited by 166 · see citing works
A cellular and regulatory map of the GABAergic nervous system of C. elegans
Gendrel, M., Atlas, E. G., & Hobert, O. (2016) · eLife · doi:10.7554/elife.17686 · Cited by 165 · see citing works
Self-citationPlasticity of the Electrical Connectome of C. elegans
Bhattacharya, A., Aghayeva, U. F., Berghoff, E. G., & Hobert, O. (2019) · Cell · doi:10.1016/j.cell.2018.12.024 · Cited by 162 · see citing works
Self-citationHirota, J., & Mombaerts, P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400940101 · Cited by 152 · see citing works
Regulatory Logic of Pan-Neuronal Gene Expression in C. elegans
Stefanakis, N., Carrera, I., & Hobert, O. (2015) · Neuron · doi:10.1016/j.neuron.2015.07.031 · Cited by 151 · see citing works
Self-citationRegulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes
Duggan, A. E., Ma, C., & Chalfie, M. (1998) · Development · doi:10.1242/dev.125.20.4107 · Cited by 144 · see citing works
Cooperative interactions enable singular olfactory receptor expression in mouse olfactory neurons
Monahan, K., Schieren, I., Cheung, J., Mumbey-Wafula, A., Monuki, E. S., & Lomvardas, S. (2017) · eLife · doi:10.7554/elife.28620 · Cited by 144 · see citing works
Genetic disruptions ofO/E2andO/E3genes reveal involvement in olfactory receptor neuron projection
Wang, S. S., Lewcock, J. W., Feinstein, P. G., Mombaerts, P., & Reed, R. R. (2004) · Development · doi:10.1242/dev.01009 · Cited by 136 · see citing works
Winnier, A. R., Meir, J. Y., Ross, J. M., Tavernarakis, N., Driscoll, M., Ishihara, T., Katsura, I., & Miller, D. M. (1999) · Genes & Development · doi:10.1101/gad.13.21.2774 · Cited by 119 · see citing works
Revisiting Neuronal Cell Type Classification in Caenorhabditis elegans
Hobert, O., Glenwinkel, L., & White, J. G. (2016) · Current Biology · doi:10.1016/j.cub.2016.10.027 · Cited by 114 · see citing works
Self-citationExpression Profiling of GABAergic Motor Neurons in Caenorhabditis elegans
Cinar, H., Keleş, S., & Jin, Y. (2005) · Current Biology · doi:10.1016/j.cub.2005.02.025 · Cited by 111 · see citing works
Brn3a and Nurr1 Mediate a Gene Regulatory Pathway for Habenula Development
Quina, L. A., Wang, S., Ng, L., & Turner, E. E. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2430-09.2009 · Cited by 110 · see citing works
Neurotransmitter Switching in the Developing and Adult Brain
Spitzer, N. C. (2017) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-072116-031204 · Cited by 109 · see citing works
A map of terminal regulators of neuronal identity in Caenorhabditis elegans
Hobert, O. (2016) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.233 · Cited by 95 · see citing works
Self-citationNeurexin directs partner-specific synaptic connectivity in C. elegans
Philbrook, A., Ramachandran, S., Lambert, C. M., Oliver, D., Florman, J., Alkema, M. J., Lemons, M. L., & Francis, M. M. (2018) · eLife · doi:10.7554/elife.35692 · Cited by 93 · see citing works
Spatiotemporal control of a novel synaptic organizer molecule
Howell, K., White, J. G., & Hobert, O. (2015) · Nature · doi:10.1038/nature14545 · Cited by 92 · see citing works
Self-citationZhang, F., Bhattacharya, A., Nelson, J. C., Abe, N., Gordon, P., Lloret-Fernández, C., Maicas, M., Flames, N., Mann, R. S., Colón‐Ramos, D. A., et al. (2013) · Development · doi:10.1242/dev.099721 · Cited by 92 · see citing works
Self-citationThe Lim homeobox geneLhx2is required for olfactory sensory neuron identity
Kolterud, Å., Alenius, M., Carlsson, L., & Bohm, S. (2004) · Development · doi:10.1242/dev.01416 · Cited by 89 · see citing works
Rhee, H. S., Closser, M., Guo, Y., Bashkirova, E., Tan, G. C., Gifford, D. K., & Wichterle, H. (2016) · Neuron · doi:10.1016/j.neuron.2016.11.037 · Cited by 86 · see citing works
Zhou, H. M., & Walthall, W. W. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-24-10438.1998 · Cited by 84 · see citing works
Serrano‐Saiz, E., Oren‐Suissa, M., Bayer, E. A., & Hobert, O. (2017) · Current Biology · doi:10.1016/j.cub.2016.11.045 · Cited by 78 · see citing works
Self-citationTranscriptional Coordination of Synaptogenesis and Neurotransmitter Signaling
Kratsios, P., Pinan-Lucarré, B., Kerk, S. Y., Weinreb, A., Bessereau, J.-L., & Hobert, O. (2015) · Current Biology · doi:10.1016/j.cub.2015.03.028 · Cited by 74 · see citing works
Self-citationSerrano‐Saiz, E., Leyva‐Díaz, E., Cruz, E. D. L., & Hobert, O. (2018) · Current Biology · doi:10.1016/j.cub.2018.06.045 · Cited by 72 · see citing works
Self-citationDiversification of C. elegans Motor Neuron Identity via Selective Effector Gene Repression
Kerk, S. Y., Kratsios, P., Hart, M. P., Mourao, R., & Hobert, O. (2017) · Neuron · doi:10.1016/j.neuron.2016.11.036 · Cited by 70 · see citing works
Self-citationThe central nervous system of ascidian larvae
Hudson, C. (2016) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.239 · Cited by 69 · see citing works
Timing mechanism of sexually dimorphic nervous system differentiation
Pereira, L., Aeschimann, F., Wang, C., Lawson, H., Serrano‐Saiz, E., Portman, D., Großhans, H., & Hobert, O. (2018) · eLife · doi:10.7554/elife.42078 · Cited by 66 · see citing works
Self-citationWyler, S. C., Spencer, W. C., Green, N. H., Rood, B. D., Crawford, L. K., Craige, C. P., Gresch, P. J., McMahon, D. G., Beck, S. G., & Deneris, E. S. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3798-15.2016 · Cited by 60 · see citing works
An intersectional gene regulatory strategy defines subclass diversity of C. elegans motor neurons
Kratsios, P., Kerk, S. Y., Catela, C., Liang, J., Vidal, B., Bayer, E. A., Feng, W., Cruz, E. D. D. L., Croci, L., Consalez, G. G., et al. (2017) · eLife · doi:10.7554/elife.25751 · Cited by 53 · see citing works
Self-citationZheng, C., Díaz-Cuadros, M., & Chalfie, M. (2015) · Neuron · doi:10.1016/j.neuron.2015.09.049 · Cited by 52 · see citing works
Single-cell transcriptome profiling of the Ciona larval brain
Sharma, S., Wang, W., & Stolfi, A. (2018) · Developmental Biology · doi:10.1016/j.ydbio.2018.09.023 · Cited by 43 · see citing works
Horie, T., Horie, R., Chen, K., Chen, C., Nakagawa, M., Kusakabe, T. G., Satoh, N., Sasakura, Y., & Levine, M. (2018) · Genes & Development · doi:10.1101/gad.317669.118 · Cited by 42 · see citing works
Convergent Transcriptional Programs Regulate cAMP Levels in C. elegans GABAergic Motor Neurons
Yu, B., Wang, X., Wei, S., Fu, T., Dzakah, E. E., Waqas, A., Walthall, W. W., & Shan, G. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.09.013 · Cited by 40 · see citing works
Masoudi, N., Tavazoie, S., Glenwinkel, L., Ryu, L., Kim, K., & Hobert, O. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2004979 · Cited by 40 · see citing works
Self-citationGabilondo, H., Stratmann, J., Irene, R.-F., et al. (2016) · PLoS Biology · doi:10.1371/journal.pbio.1002450 · Cited by 39 · see citing works
Alqadah, A., Hsieh, Y., Vidal, B., Chang, C., Hobert, O., & Chuang, C. (2015) · The EMBO Journal · doi:10.15252/embj.201592188 · Cited by 38 · see citing works
Self-citationLhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons
Zhang, G., Titlow, W. B., Biecker, S. M., et al. (2016) · eNeuro · doi:10.1523/eneuro.0230-16.2016 · Cited by 25 · see citing works
Stratmann, J., & Thor, S. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006729 · Cited by 25 · see citing works
Kim, J., Yeon, J., Choi, S., Huh, Y. H., Fang, Z., Park, S. J., Kim, M. O., Ryoo, Z. Y., Kang, K., Kweon, H., et al. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005480 · Cited by 24 · see citing works
Terminal Differentiation of Mesodiencephalic Dopaminergic Neurons:
Smidt, M. P., Burbach, J. P. H., & Burbach, H. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-0322-8_4 · Cited by 23 · see citing works
Terminal differentiation ofmesodiencephalic dopaminergic neurons: the role of Nurr1 and Pitx3.
Smidt, M. P., & Burbach, J. P. H. (2009) · PubMed · Cited by 22 · see citing works
Zheng, C., Jin, F. Q., Trippe, B. L., Wu, J., & Chalfie, M. (2018) · Development · doi:10.1242/dev.168096 · Cited by 13 · see citing works
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- Authors
- Hobert, O., & Kratsios, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of Chicago (US)
- Corresponding author
- Hobert, Oliver
- Kratsios, Paschalis
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 56
- Pages
- 97-105
- ISSN
- 0959-4388 (ISSN-L)
- OpenAlex
- W2910337627
- Cited by
- 169
- References
- 53
- Citations by year
- 2026: 19 · 2025: 19 · 2024: 24 · 2023: 20 · 2022: 38 · 2021: 22 · 2020: 23 · 2019: 4
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NINDS (R00NS084988)
- Whitehall Foundation (5R37NS039996)
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- neuronal identity, terminal differentiation, transcription factors, Caenorhabditis elegans, Drosophila, Chordata, neuroplasticity, postmitotic neurons
- MeSH terms
- Animals, Cell Differentiation, Diptera, Neurons, Gene Expression Regulation, Developmental, Caenorhabditis elegans Proteins, Chordata
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