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Dopamine Modulates Cell Cycle in the Lateral Ganglionic Eminence
Open accessAbstract
Dopamine is a neuromodulator the functions of which in the regulation of complex behaviors such as mood, motivation, and attention are well known. Dopamine appears in the brain early in the embryonic period when none of those behaviors is robust, raising the possibility that dopamine may influence brain development. The effects of dopamine on specific developmental processes such as neurogenesis are not fully characterized. The neostriatum is a dopamine-rich region of the developing and mature brain. If dopamine influenced neurogenesis, the effects would likely be pronounced in the neostriatum. Therefore, we examined whether dopamine influenced neostriatal neurogenesis by influencing the cell cycle of progenitor cells in the lateral ganglionic eminence (LGE), the neuroepithelial precursor of the neostriatum. We show that dopamine arrives in the LGE via the nigrostriatal pathway early in the embryonic period and that neostriatal neurogenesis progresses in a dopamine-rich milieu. Dopamine D1-like receptor activation reduces entry of progenitor cells from the G 1 - to S-phase of the cell cycle, whereas D2-like receptor activation produces the opposite effects by promoting G 1 - to S-phase entry. D1-like effects are prominent in the ventricular zone, and D2-like effects are prominent in the subventricular zone. The overall effects of dopamine on the cell cycle are D1-like effects, most likely because of the preponderance of D1-like binding sites in the embryonic neostriatum. These data reveal a novel developmental role for dopamine and underscore the relevance of dopaminergic signaling in brain development.
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“It has furthermore been shown that dopamine and GABA interactions can influence these processes [187, 188].”
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“Indeed, early embryonic dopamine has been shown to modulate cell cycle regulation in the murine LGE, resulting in an increase in cell output (Ohtani et al. 2003).”
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“The effect of D1-receptor activation is dominant over the effect of the D2 receptor and results in an overall reduction of cells entering S-phase (Ohtani et al., 2003).”
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“Trophic functions of neurotransmitters on neural stem cells are noted during development (Ohtani et al., 2003) and in the postnatal brain (Berg et al., 2013; Borta and Höglinger, 2007).”
BackgroundNeurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a Parkinson’s Disease Model
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“…dopamine receptor activation can influence neurogenesis, neuronal migration and differentiation in the embryonic brain (Zhang and Lidow, 2002, Ohtani et al., 2003, Popolo et al., 2004, Stanwood et al., 2005, Zhang et al., 2005, Crandall et al., 2007) and neurogenesis in the mature brain…”
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“…through D2R activation in the entry from the G1 to the S-phase in SVZ progenitor cells (Type C cells probably), whereas the activation of D1R might produce opposite effects (Doetsch et al., 2002; Höglinger et al., 2004; Kippin et al., 2005; Ohtani et al., 2003; O'Keeffe, Barker, & Caldwell, 2009).”
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Metadata
- Authors
- Ohtani, N., Goto, T., Waeber, C., & Bhide, P. G.
- Affiliations
- Pediatrics and Genetics (US)
- Harvard University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-04-01
- Volume
- 23
- Issue
- 7
- Pages
- 2840-2850
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC1201391
- OpenAlex
- W2150700826
- Semantic Scholar
- 5c05744728753731ef7333746826dd9b22331c10
- Cited by
- 193
- References
- 68
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 9 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 3 · 2014: 8 · 2013: 10 · 2012: 12
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- U.S. Public Health Service (HD 05515)
- National Institute of Neurological Disorders and Stroke (NS 43426, NS 62005, R01NS043426)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD005515, HD05515)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- dopamine, lateral ganglionic eminence, neostriatum, cell cycle, neurogenesis, D1-like receptors, D2-like receptors, progenitor cells, G1/S transition, nigrostriatal pathway, subventricular zone, ventricular zone, brain development, embryonic development
- MeSH terms
- Animals, Bromodeoxyuridine, Cell Cycle, Cell Division, Dopamine, Ganglia, Neurons, Stem Cells, Neostriatum, Receptors, Dopamine D1, Receptors, Dopamine D2, Culture Techniques, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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