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Local and Global Spontaneous Calcium Events Regulate Neurite Outgrowth and Onset of GABAergic Phenotype during Neural Precursor Differentiation
Open accessAbstract
Neural stem cells can generate in vitro progenitors of the three main cell lineages found in the CNS. The signaling pathways underlying the acquisition of differentiated phenotypes in these cells are poorly understood. Here we tested the hypothesis that Ca(2+) signaling controls differentiation of neural precursors. We found low-frequency global and local Ca(2+) transients occurring predominantly during early stages of differentiation. Spontaneous Ca(2+) signals in individual precursors were not synchronized with Ca(2+) transients in surrounding cells. Experimentally induced changes in the frequency of local Ca(2+) signals and global Ca(2+) rises correlated positively with neurite outgrowth and the onset of GABAergic neurotransmitter phenotype, respectively. NMDA receptor activity was critical for alterations in neuronal morphology but not for the timing of the acquisition of the neurotransmitter phenotype. Thus, spontaneous Ca(2+) signals are an intrinsic property of differentiating neurosphere-derived precursors. Their frequency may specify neuronal morphology and acquisition of neurotransmitter phenotype.
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“These findings support our model in which CYFIP1 regulation of calcium channel subunits compromise intracellular calcium levels, resulting in delayed axonal development10,84,85 (Fig. 7).”
From CYFIP1 governs the development of cortical axons by modulating calcium availability (2025) · cites this paper as [84]
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Items 101–113 of 113
Fruehauf, S., & Ho, A. D. (2005) · Cytotherapy · doi:10.1080/14653240510027208 · Cited by 5
Ávila, D., Aedo, E., Sánchez-Hechavarría, M. E., Ávila, C., & Ávila, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218013 · Cited by 6
“It has been reported that this type of calcium activity can participate in cell fate determination, cell proliferation [29,36], neurogenesis, cell migration [6,7,16], morphological maturation [37] and neuronal specification [28,38,39].”
BackgroundMORPHOLESS NEURONS COMPROMISE THE DEVELOPMENT OF CORTICAL CONNECTIVITY
Gafarov, F. M., Khusnutdinov, N., & Galimyanov, F. (2009) · Journal of Integrative Neuroscience · doi:10.1142/s0219635209002058 · Cited by 4
“[27] Ciccolini F, Collins TJ, Sudhoelter J, Lipp P, Berridge MJ, Local and Global Spontaneous Calcium Events Regulate Neurite Outgrowth and Onset of GABAergic Phenotype during Neural Precursor Differentiation, J.”
BackgroundEthanol Modulates Spontaneous Calcium Waves in Axonal Growth Cones in Vitro
Lindsley, T. A., & Mazurkiewicz, J. (2013) · Brain Science · doi:10.3390/brainsci3020615 · Cited by 3
“When localized waves in cell bodies and in growth cones are counted, about 38% of embryonic Xenopus spinal neurons display Ca 2+ waves during 60 min period [19] and 50% of differentiating mouse striatal neurospheres show waves over 10 min [20].”
BackgroundActivation of GABAAreceptors suppresses ethanol‐induced upregulation of type 1 IP3receptors
Mizuno, K., Kurokawa, K., & Ohkuma, S. (2012) · Synapse · doi:10.1002/syn.21610 · Cited by 4
Insights into GABA functions in the developing cerebellum
Fiszman, M. L. (2005) · International review of neurobiology · doi:10.1016/s0074-7742(05)71004-7 · Cited by 4
Ablondi, E. F., Paudel, S., Sehdev, M., Marken, J. P., Halleran, A. D., Rahman, A., Kemper, P., & Saha, M. (2020) · Journal of Visualized Experiments · doi:10.3791/60726 · Cited by 2
CYFIP1 governs the development of cortical axons by modulating calcium availability
Ricci, C., Midroit, M. J., Caicci, F., Achsel, T., Domínguez-Iturza, N., & Bagni, C. (2025) · Nature Communications · doi:10.1038/s41467-025-65801-0 · Cited by 1
“While some studies have reported that a sudden calcium increase in growth cones negatively regulates axon extension 80 – 83 , others have found that elevating [Ca 2+ ] promotes outgrowth 84 .”
Zavala, M., Ghosh, A., Joseph, S. K., & Chakrabarti, R. (2026) · bioRxiv · doi:10.64898/2026.04.09.717539 · Cited by 1
Neural stem cells-from quiescence to differentiation and potential clinical uses
Dobranici, A., Dinescu, S., & Costache, M. (2021) · Reviews in Biological and Biomedical Sciences · doi:10.31178/rbbs.2021.4.1.2
Studies of ionic mechanisms in model cell lines of prostate cancer
Rizaner, N. (2010) · doi:10.25560/8992
“, 2003), development of neurotransmitter phenotype (Ciccolini et al., 2003), formation of nodules in plant root hairs (Ehrhardt et al.”
BackgroundMechanisms of Synapse Formation: Activity-Dependent Selection of Neurotransmitters and Receptors
Borodinsky, L. N., & Spitzer, N. (2009) · Springer eBooks · doi:10.1007/978-0-387-09622-3_3
“The influence of electrical activity in neurotransmitter specification applies to GABA (Hendry and Jones, 1986, 1988; Akbarian et al., 1995; Gu and Spitzer, 1995; Watt et al., 2000; Ramirez and Gutierrez, 2001; Gutierrez, 2002; Ciccolini et al., 2003; Gutierrez et al., 2003; Patz et al., 2003; Borodinsky et al., 2004;…”
Background
Metadata
- Authors
- Ciccolini, F., Collins, T. J., Sudhoelter, J., Lipp, P., Berridge, M. J., & Bootman, M. D.
- Affiliations
- Babraham Institute (GB)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-01-01
- Volume
- 23
- Issue
- 1
- Pages
- 103-111
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6742163
- OpenAlex
- W2159977558
- Cited by
- 135
- References
- 36
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 7 · 2013: 13 · 2012: 11
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Research Online - ORO (The Open University) (acceptedVersion)
- Funders
- Directorate for Biological Sciences
- Merck Sharp and Dohme
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- calcium signaling, neural precursor differentiation, neurite outgrowth, NMDA receptor, neuronal morphology, calcium transients
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Central Nervous System, gamma-Aminobutyric Acid, Kinetics, Neurons, Phenotype, Potassium Chloride, Stem Cells, Receptors, N-Methyl-D-Aspartate, Neurites, Calcium Signaling, Mice
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