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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CYFIP1 regulation of calcium channel subunits compromises intracellular calcium levels, resulting in delayed axonal development.
“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]
The Results section (page not specified in our copy) reports that low-calcium conditions significantly shortened neurites in differentiating neural precursors. That supports the calcium–outgrowth link, but the paper does not establish that CYFIP1 regulates calcium-channel subunits or that this mechanism delays axonal development. (LLM, conf=0.88)
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Berridge, M., Bootman, M., & Roderick, H. (2003) · Nature reviews. Molecular cell biology · doi:10.1038/nrm1155 · Cited by 5,747 · see citing works
Self-citationThe molecular basis for calcium-dependent axon pathfinding
Gomez, T. M., & Zheng, J. Q. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1844 · Cited by 330 · see citing works
“However, other studies have found that elevating [Ca 2+ ] i in growth cones promotes neurite outgrowt”
BackgroundFundamentals of Cellular Calcium Signaling: A Primer.Preprint
Bootman, M., & Bultynck, G. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a038802 · Cited by 302 · see citing works
“Alternatively, Ca 2+ signaling can occur because of intrinsic cellular cues, such as the spontaneous Ca 2+ signals within cardiac myocytes (Hüser et al. 2000) and developing neurons (Ciccolini et al. 2003).”
BackgroundSelf-citationRegionalization and fate specification in neurospheres: the role of Olig2 and Pax6.
Hack, M., Sugimori, M., Lundberg, C., Nakafuku, M., & Götz, M. (2004) · Molecular and cellular neurosciences · doi:10.1016/j.mcn.2003.12.012 · Cited by 294 · see citing works
Ju, B., Solum, D., Song, E. J., Lee, K.-J., Rose, D., Glass, C., & Rosenfeld, M. (2004) · Cell · doi:10.1016/j.cell.2004.11.017 · Cited by 285 · see citing works
A Noncanonical Release of GABA and Glutamate Modulates Neuronal Migration
Manent, J.-B., Demarque, M., Jorquera, I., Pellegrino, C., Ben-Ari, Y., Aniksztejn, L., & Represa, A. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0553-05.2005 · Cited by 220 · see citing works
“However, spontaneous activity has been shown to result in calcium transients and to be critical for neurite outgrowth and pathfinding (Spitzer et al., 2000; Ciccolini et al., 2003; Tang et al., 2003).”
BackgroundSchreiber, T., Gassmann, K., Götz, C., Hübenthal, U., Moors, M., Krause, G., Merk, H., Nguyen, N., Scanlan, T., Abel, J., et al. (2009) · Environmental Health Perspectives · doi:10.1289/ehp.0901435 · Cited by 208 · see citing works
“Calcium signaling is a key player in developmental processes (Ciccolini et al. 2003; Greer and Greenberg 2008), and BDE47 disturbs calcium homeostasis in rat PC12 pheochromocytoma cells after 20 min of exposure (Dingemans et al. 2008).”
BackgroundAltered differentiation of neural stem cells in fragile X syndrome
Castrén, M., Tervonen, T., Kärkkäinen, V., Heinonen, S., Castrén, E., Larsson, K., Bakker, C. E., Oostra, B. A., & Åkerman, K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508995102 · Cited by 176 · see citing works
Jablonka, S., Beck, M., Lechner, B. D., Mayer, C., & Sendtner, M. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200703187 · Cited by 172 · see citing works
“…on laminin-111, spontaneous spikelike Ca2+ transients were detectable that appeared synchronized in the cell body, dendrites, axons, and axonal growth cones, thus refl ecting global spontaneous depolarization as described previously for developing neurons (Gu et al., 1994; Ciccolini et al., 2003).”
BackgroundLocal calcium transients regulate the spontaneous motility of dendritic filopodia
Lohmann, C., Finski, A., & Bonhoeffer, T. (2005) · Nature Neuroscience · doi:10.1038/nn1406 · Cited by 157 · see citing works
Regulation of dendritic growth and plasticity by local and global calcium dynamics.
Lohmann, C., & Wong, R. O. (2005) · Cell Calcium · doi:10.1016/j.ceca.2005.01.008 · Cited by 146 · see citing works
Schlecker, C., Boehmerle, W., Jeromin, A., DeGray, B., Varshney, A., Sharma, Y., Szigeti‐Buck, K., & Ehrlich, B. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci22466 · Cited by 157 · see citing works
Stem Cells and Calcium Signaling
Tonelli, F. M. P., Santos, A. K., Gomes, D. A., Silva, S. L. D., Gomes, K. N., Ladeira, L. O., & Resende, R. R. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2888-2_40 · Cited by 138 · see citing works
“Some discussion and works involving the Gαi/o-coupled receptors demonstrated that, activation of this signaling pathway, generating cAMP, would lead carcinoma stem cells to differentiate into neuronal cells [42, 71], and neural stem cells to regulate neurite outgrowth [72].”
BackgroundScemes, E., Duval, N., & Meda, P. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-36-11444.2003 · Cited by 133 · see citing works
“Similar results were described recently for neurosphere-derived precursors in which the percentage of cells displaying both global and local spontaneous calcium oscillations was greater during the first 2 d of development, decreasing over time as the cells differentiated into neuronal and glial phenotypes (Ciccolini e…”
ResultOrchestrating neuronal differentiation: patterns of Ca2+ spikes specify transmitter choice.
Spitzer, N., Root, C. M., & Borodinsky, L. N. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.05.003 · Cited by 132 · see citing works
Gakhar‐Koppole, N., Hundeshagen, P., Mandl, C., Weyer, S., Allinquant, B., Müller, U., & Ciccolini, F. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06398.x · Cited by 129 · see citing works
“have previously shown that spontaneous and depolarization induced calcium influx similarly promote neurite outgrowth in neurons differentiating from embryonic neural precursors (NPCs) and that this process requires N-methyl-d-aspartic acid receptor (NMDAR) activation (Ciccolini et al., 2003).”
BackgroundResultInfluentialSelf-citationJansson, L. C., & Åkerman, K. E. O. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1174-6 · Cited by 124 · see citing works
“Ca2? signaling in the cell is a complex process and coupled to cellular events such as differentiation, migration, neurite outgrowth and growth cone dynamics (Ciccolini et al. 2003; Gomez and Zheng 2006; Zheng and Poo 2007).”
BackgroundInfluentialMitochondrial Ca2+ signals in autophagy
Cárdenas, C., & Foskett, J. (2012) · Cell Calcium · doi:10.1016/j.ceca.2012.03.001 · Cited by 114 · see citing works
Neural progenitors organize in small-world networks to promote cell proliferation
Malmersjö, S., Rebellato, P., Smedler, E., Planert, H., Kanatani, S., Liste, I., Nanou, E., Sunner, H., Abdelhady, S., Zhang, S., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220179110 · Cited by 104 · see citing works
“, without externally applied stimuli) electrical and chemical activity (15, 16).”
BackgroundCompletion of neuronal migration regulated by loss of Ca(2+) transients.
Kumada, T., & Komuro, H. (2004) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0401000101 · Cited by 107 · see citing works
Calcium signaling in specialized glial cells
Metea, M. R., & Newman, E. A. (2006) · Glia · doi:10.1002/glia.20352 · Cited by 100 · see citing works
“In neurospherederived precursor striatal cells, Ca21 signaling controls neurite outgrowth and acquisition of a neurotransmitter phenotype (Ciccolini et al., 2003).”
BackgroundProgrammed and Induced Phenotype of the Hippocampal Granule Cells
Gómez-Lira, G., Lamas, M., Romo-Parra, H., & Gutiérrez, R. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1674-05.2005 · Cited by 99 · see citing works
“The role of calcium on phenotypic differentiation, and especially on the expression of the GABAergic phenotype, has been documented in developing cells (Watt et al., 2000; Ciccolini et al., 2003; Borodinsky et al., 2004).”
BackgroundBDNF and TrkB in neuronal differentiation of Fmr1-knockout mouse
Louhivuori, V., Vicario, A., Uutela, M., Rantamäki, T., Louhivuori, L. M., Ċastrén, E., Tongiorgi, E., Åkerman, K. E. O., & Castrén, M. L. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.10.018 · Cited by 89 · see citing works
“Enhanced calcium responses to BDNF and ATP in NPCs lacking FMRP Changes in intracellular free Ca2+ play an important role in the differentiation of NPCs (Ciccolini et al. 2003, Kärkkäinen et al., 2009).”
BackgroundLiao, C.-Y., Li, X.-Y., Wu, B., Duan, S., & Jiang, G.-B. (2008) · Environmental Science & Technology · doi:10.1021/es800018k · Cited by 96 · see citing works
Bosch, M., Pineda, J. R., Suñol, C., Petriz, J., Cattaneo, E., Alberch, J., & Canals, J. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.06.027 · Cited by 83 · see citing works
“These findings agree with previous studies showing the effect of KCl-induced depolarization and global spontaneous calcium spikes on the GABAergic phenotype in neurosphere-derived precursors (Ciccolini et al., 2003) and embryonic Xenopus spinal cord neurons (Gu and Spitzer, 1995; Spitzer et al.”
BackgroundResultRibiczey, P., Tordai, A., Andrikovics, H., Filoteo, A. G., Penniston, J. T., Enouf, J., Enyedi, Á., Papp, B., & Kovàcs, T. (2007) · Cell Calcium · doi:10.1016/j.ceca.2007.02.003 · Cited by 77 · see citing works
“Changes of Ca2+ signaling and handling control also muscle development [65], neuronal precursor differentiation [66,67], osteoblast growth and differentiation [68].”
BackgroundAxon diameter and axonal transport: In vivo and in vitro effects of androgens
Pesaresi, M., Soon-Shiong, R., French, L., Kaplan, D., Miller, F., & Paus, T. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.04.048 · Cited by 73 · see citing works
Moccia, F., Lodola, F., Dragoni, S., Bonetti, E., Bottino, C., Guerra, G., Laforenza, U., Rosti, V., & Tanzi, F. (2014) · Current Vascular Pharmacology · doi:10.2174/157016111201140327162858 · Cited by 72 · see citing works
“In addition, spontaneous Ca 2+ signals specify neuronal morphology and dictate neurotransmitter choice in mice neuronal progenitor cells [120], whereas the onset of Ca 2+ spiking is a pre-requisite for adult liver stem cells to acquire a myocardial phenotype [121].”
BackgroundHolmes, S., Abbassi, B., Su, C., Singh, M., & Cunningham, R. (2013) · Endocrinology · doi:10.1210/en.2013-1242 · Cited by 71 · see citing works
Berridge, M. J. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00188.2017 · Cited by 74 · see citing works
Self-citationWan Ibrahim, W. N., Tofighi, R., Onishchenko, N., Rebellato, P., Bose, R., Uhlén, P., & Ceccatelli, S. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.03.003 · Cited by 65 · see citing works
Sunamura, N., Iwashita, S., Enomoto, K., Kadoshima, T., & Isono, F. (2018) · Scientific Reports · doi:10.1038/s41598-018-30025-4 · Cited by 62 · see citing works
Timing in Cellular Ca2+ Signaling
Boulware, M. J., & Marchant, J. S. (2008) · Current Biology · doi:10.1016/j.cub.2008.07.018 · Cited by 62 · see citing works
“Ca2+ signals observed during cellular differentiation [6,23,24], reinforce differentiative events and possibly impact their intrinsic timing.”
Majumder, P., Trujillo, C. A., Lopes, C. G., Resende, R., Gomes, K. N., Yuahasi, K., Britto, L., & Ulrich, H. (2007) · Purinergic Signalling Purinergic Signalling · doi:10.1007/s11302-007-9074-y · Cited by 59 · see citing works
“Moreover, the importance of calcium signaling for differentiation of NPC has been studied [67, 68], and direct evidence for the participation of P2Y1 receptor-activated pathways in the early development has been provided by Scemes et al.”
BackgroundResende, R. R., Alves, A. S., Britto, L. R. G., & Ulrich, H. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.01.003 · Cited by 58 · see citing works
Warm, D., Schroer, J., & Sinning, A. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.807969 · Cited by 60 · see citing works
“Meanwhile, spontaneous calcium activity in parallel also critically impacts the further specification of neuronal phenotypes (Ciccolini et al., 2003; Borodinsky et al., 2004), which is no surprise considering the tight link between neuronal gene expression and neuronal activity (Flavell and Greenberg, 2008).”
BackgroundGlaser, T., Resende, R., & Ulrich, H. (2013) · Cell Communication and Signaling · doi:10.1186/1478-811x-11-12 · Cited by 55 · see citing works
“Surprisingly, spontaneous Ca signals in individual precursors were not synchronized with Ca transients in surrounding cells, indicating the existence of a different pathway, not depending on connexin 43-hemichannel-mediated intercellular Ca signaling [41].”
BackgroundMironov, S., Skorova, E., Hartelt, N., Mironova, L. A., Hasan, M. T., & Kügler, S. (2009) · Journal of Physiology · doi:10.1113/jphysiol.2009.169805 · Cited by 54 · see citing works
“calcium increases promote their repulsion (Wong & Ghosh, 2002; Ciccolini et al. 2003; Henley & Poo, 2004; McAllister, 2007).”
BackgroundCesetti, T., Obernier, K., Bengtson, C., Fila, T., Mandl, C., Hölzl-Wenig, G., Wörner, K., Eckstein, V., & Ciccolini, F. (2009) · Stem Cells · doi:10.1002/stem.74 · Cited by 54 · see citing works
Self-citationDendritic plasticity of CA1 pyramidal neurons after transient global ischemia
Ruan, Y., Zou, B., Fan, Y., Li, Y., Lin, N., Zeng, Y., Gao, T.-M., Yao, Z., & Xu, Z. C. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.01.039 · Cited by 52 · see citing works
Long-term consequences of prenatal stress and neurotoxicants exposure on neurodevelopment
Antonelli, M. C., Pallarés, M. E., Ceccatelli, S., & Spulber, S. D. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.05.005 · Cited by 60 · see citing works
Diversity of LPA receptor-mediated intracellular calcium signaling in early cortical neurogenesis
Dubin, A. E., Herr, D., & Chun, J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.6151-09.2010 · Cited by 52 · see citing works
“…(Gu and Spitzer, 1995; Behar et al., 1996, 1999; Komuro and Rakic, 1998; Flint et al., 1999; Maric et al., 2000a; Owens et al., 2000; Opitz et al., 2002; Ciccolini et al., 2003; Spitzer et al., 2004; Weissman et al., 2004; Calderon et al., 2005; Komuro and Kumada, 2005; Kumada et al., 2006).”
BackgroundLiu, X., Kelsoe, J. R., & Greenwood, T. A. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.09.029 · Cited by 56 · see citing works
“…plays a crucial role in the regulation of neurotransmitter release, synaptic plasticity, neurite outgrowth, and neurodegeneration (Berridge, 1998; Ciccolini et al., 2003), and several studies have suggested an altered calcium homeostasis in the pathophysiology of bipolar disorder (Emamghoreishi…”
Role of Nav1.9 in activity-dependent axon growth in motoneurons
Subramanian, N., Wetzel, A., Dombert, B., Yadav, P., Havlicek, S., Jablonka, S., Nassar, M. A., Blum, R., & Sendtner, M. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds195 · Cited by 45 · see citing works
Physiology of Ca(2+) signalling in stem cells of different origins and differentiation stages.
Forostyak, O., Forostyak, S., Kortus, S., Sykova, E., Verkhratsky, A., & Dayanithi, G. (2016) · Cell Calcium · doi:10.1016/j.ceca.2016.02.001 · Cited by 49 · see citing works
Opposite regulatory effects of TRPC1 and TRPC5 on neurite outgrowth in PC12 cells.
Heo, D. K., Chung, W.-Y., Park, H., Yuan, J. P., Lee, M. G., & Kim, J. Y. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2011.12.011 · Cited by 49 · see citing works
Zhou, C., Wen, Z.-X., Shi, D.-M., & Xie, Z.-P. (2004) · Cell Biology International · doi:10.1016/j.cellbi.2003.10.005 · Cited by 47
“As the role of mAchR in inducing NSC proliferation and differentiation in vitro has been established, further study will focus on details of the association between calcium transients and NSC differentiation (Ciccolini et al., 2003).”
BackgroundMoccia, F., Bonetti, E., Dragoni, S., Fontana, J., Lodola, F., Romani, R., Laforenza, U., Rosti, V., & Tanzi, F. (2012) · Current Signal Transduction Therapy · doi:10.2174/157436212800376672 · Cited by 45 · see citing works
Phosphatidylcholine restores neuronal plasticity of neural stem cells under inflammatory stress
Magaquian, D., Delgado‐Ocaña, S., Perez, C., & Banchio, C. (2021) · Scientific Reports · doi:10.1038/s41598-021-02361-5 · Cited by 47 · see citing works
Gassmann, K., Schreiber, T., Dingemans, M., Krause, G., Roderigo, C., Giersiefer, S., Schuwald, J., Moors, M., Unfried, K., Bergman, A., et al. (2014) · Archives of Toxicology · doi:10.1007/s00204-014-1217-7 · Cited by 42 · see citing works
“ca2+ is an earlyresponse second messenger and as such plays a key role in a number of physiological processes including cell proliferation, differentiation and apoptosis as well as a wide variety of specific neuronal processes including dendritic spine growth, synaptic plasticity and neurotransmission (Berridge et al.…”
Homeostatic activity-dependent paradigm for neurotransmitter specification.
Spitzer, N., Borodinsky, L. N., & Root, C. M. (2005) · Cell Calcium · doi:10.1016/j.ceca.2005.01.021 · Cited by 42
Monitoring neuronal calcium signalling using a new method for ratiometric confocal calcium imaging.
Lohr, C. (2003) · Cell Calcium · doi:10.1016/s0143-4160(03)00105-2 · Cited by 40
“transients in growth cones in frog and mouse [25,26].”
BackgroundRole of calcium and kinases on the neurotrophic effect induced by γ‐aminobutyric acid
Fiszman, M., & Schousboe, A. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20062 · Cited by 37 · see citing works
“…affect several parameters of neuronal maturation, such as phenotypic expression, dendritic arbor complexity, axon guidance, and synaptic strength (Mattson et al., 1988; Rajan and Cline, 1998; Gomez and Spitzer, 1999; Wu et al., 1999; Wilson et al., 2000; Sin et al., 2002; Ciccolini et al., 2003).”
BackgroundExpression of calcium transporters in the retina of the tiger salamander (Ambystoma tigrinum)
Križaj, D., Liu, X., & Copenhagen, D. (2004) · The Journal of comparative neurology · doi:10.1002/cne.20170 · Cited by 35
“Because Ca2 -regulated pathways can distinguish between calcium signals of differing properties, Ca2 can control a variety of different functions in different parts of the cell (Delmas and Brown, 2003).”
BackgroundRelationship between GABAergic interneurons migration and early neocortical network activity
de Lima, A. D., Gieseler, A., & Voigt, T. (2009) · Developmental Neurobiology · doi:10.1002/dneu.20696 · Cited by 34 · see citing works
Smedler, E., Louhivuori, L., Romanov, R. A., Masini, D., Dehnisch Ellström, I., Wang, C., Caramia, M., West, Z., Zhang, S., Rebellato, P., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2108768119 · Cited by 34 · see citing works
Effect of glutamate receptor antagonists on migrating neural progenitor cells
Jansson, L., Louhivuori, L., Wigren, H., Nordström, T., Louhivuori, V., Castrén, M., & Åkerman, K. E. O. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12152 · Cited by 33 · see citing works
“The extension of neurites in progenitor cells appears to be controlled by the frequency of Ca signals rather than tonic Ca elevations (Ciccolini et al., 2003).”
BackgroundJansson, L., Louhivuori, L., Wigren, H., Nordström, T., Louhivuori, V., Castrén, M. L., & Åkerman, K. E. O. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.08.038 · Cited by 31 · see citing works
“NMDA receptors, however, seem to dominate at later stages of differentiation in postnatal hippocampal progenitors (Ciccolini et al., 2003; Deisseroth et al., 2004).”
GABA Not Only a Neurotransmitter: Osmotic Regulation by GABAAR Signaling
Cesetti, T., Ciccolini, F., & Li, Y. (2012) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2012.00003 · Cited by 27 · see citing works
Self-citationBeutler, L. R., Eldred, K. C., Quintana, A., Keene, C. D., Rose, S. E., Postupna, N. O., Montine, T. J., & Palmiter, R. D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028168 · Cited by 32 · see citing works
“In addition to their role in transmitting glutamate signals in mature animals during learning, NMDARs have been implicated in neuronal development in several brain regions [21–23].”
Neurotransmitter responsiveness during early maturation of neural progenitor cells.
Kärkkäinen, V., Louhivuori, V., Castrén, M., & Åkerman, K. (2009) · Differentiation; research in biological diversity · doi:10.1016/j.diff.2008.10.005 · Cited by 31 · see citing works
“In particular, changes (receptor-mediated) in intracellular Ca are known to be important intracellular signals in such responses (Ciccolini et al., 2003).”
BackgroundInfluentialSecondo, A., Esposito, A., Sirabella, R., Boscia, F., Pannaccione, A., Molinaro, P., Cantile, M., Ciccone, R., Sisalli, M., Scorziello, A., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.555516 · Cited by 29
“(29) reported that neurons become increasingly competent at Ca(2) signaling as differentiation proceeds and show an increased amount of Ca(2) in the ER in the late phase of the process (29).”
BackgroundIn Vivo Calcium Dynamics During Neural Crest Cell Migration and Patterning Using GCaMP3
McKinney, M. C., & Kulesa, P. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.08.004 · Cited by 29 · see citing works
“Thus, our in vivo temporal measurements of NC cell calcium transients were comparable with recorded measurements in other cell types (Ciccolini et al., 2003; Gu and Spitzer, 1995; O'Donovan, 1999), but had unique dynamics compared to in vitro NC cell analysis.”
González‐Cota, A. L., Martínez-Flores, D., Rosendo‐Pineda, M. J., & Vaca, L. A. (2024) · Cell Calcium · doi:10.1016/j.ceca.2024.102856 · Cited by 38 · see citing works
Glaser, T., Shimojo, H., Ribeiro, D., Martins, P., Beco, R., Kosinski, M., Sampaio, V., Corrêa-Velloso, J. C., Oliveira-Giacomelli, Á., Lameu, C., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0717-5 · Cited by 28
“[63] reported that P2 receptor activation increases neurite extension and GABAergic differentiation.”
BackgroundIntracellular Ca²⁺ Signals to Reconstruct A Broken Heart: Still A Theoretical Approach?
Moccia, F., Ruffinatti, F., & Zuccolo, E. (2015) · Current Drug Targets · doi:10.2174/1389450116666141219121723 · Cited by 28 · see citing works
Tofighi, R., Ibrahim, W. N. W., Rebellato, P., Andersson, P., Uhlén, P., & Ceccatelli, S. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr221 · Cited by 28 · see citing works
“This has been shown in mouse primary culture of NSCs from embryonic day 14 where both global and local spontaneous Ca2þ signals were shown to be more frequent at early stages of neural precursor differentiation (Ciccolini et al., 2003).”
BackgroundNitric Oxide–mediated Modulation of Synaptic Activity by Astrocytic P2Y Receptors
Mehta, B., Begum, G., Joshi, N. B., & Joshi, P. G. (2008) · The Journal of General Physiology · doi:10.1085/jgp.200810043 · Cited by 29 · see citing works
“Local and global spontaneous Ca 2+ oscillations are key regulators for onset of neuronal phenotype during neural precursor differentiation and cell specifi cation in the developing nervous system ( Ciccolini et al., 2003 ).”
BackgroundLam, B., & Chawla, S. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.09.030 · Cited by 27 · see citing works
Abematsu, M., Kagawa, T., Fukuda, S., Inoue, T., Takebayashi, H., Komiya, S., & Taga, T. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20762 · Cited by 26 · see citing works
“An intriguing observation is that neurosphere-forming cells from various regions generate mostly GABAergic neurons (Hitoshi et al., 2002; Parmar et al., 2002; Ciccolini et al., 2003; Hack et al., 2004).”
BackgroundSpatiotemporal integration of developmental cues in neural development
Borodinsky, L. N., Belgacem, Y. H., Swapna, I., Visina, O., Balashova, O., Sequerra, E., Tu, M. K., Levin, J. B., Spencer, K., Castro, P. A., et al. (2014) · Developmental Neurobiology · doi:10.1002/dneu.22254 · Cited by 24 · see citing works
“, 2003) to neurotransmitter specification (Gu and Spitzer, 1995; Ciccolini et al., 2003; Borodinsky et al., 2004).”
BackgroundInfluentialYu, H., Wen, J., Wang, R., Shen, W., Duan, S., & Yang, H. (2007) · Cell Calcium · doi:10.1016/j.ceca.2007.07.006 · Cited by 22 · see citing works
Bikbaev, A. F., Ciuraszkiewicz, A., Heck, J., Klatt, O., Freund, R., Mitlöhner, J., Lacalle, S. E., Sun, M., Repetto, D., Frischknecht, R., et al. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.1707-19.2020 · Cited by 40 · see citing works
“These outcomes corroborate previous reports showing an important role of spontaneous Ca21 transients in regulation of the neurite outgrowth and branching (Ciccolini et al., 2003) and structural maturation of synapses (Choi et al., 2014).”
ResultViero, C., & Dayanithi, G. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(08)00416-0 · Cited by 23 · see citing works
“Intracellular Ca concentration [Ca]i changes play a major role in the control of several neuronal functions (Burgoyne, 2007), notably during the development of the CNS (Ciccolini et al., 2003; Zamoner et al., 2007) and the PNS (Dayanithi et al.”
BackgroundInfluentialANO1/TMEM16A regulates process maturation in radial glial cells in the developing brain
Hong, G., Lee, S. H., Lee, B., Choi, J. H., Oh, S., Jang, Y., Hwang, E. M., Kim, H., Jung, J., Kim, I., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901067116 · Cited by 24 · see citing works
“Spontaneous Ca spikes are observed in cultured neural precursor cells and are correlated with neurite length (9).”
BackgroundGaleotti, N., Vivoli, E., Norcini, M., Bartolini, A., & Ghelardini, C. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.029 · Cited by 19 · see citing works
“Calcium is a ubiquitous intracellular signalling molecule that is required for initiating and regulating a wide range of neuronal functions, including neurotransmitter release, synaptic plasticity, neurite outgrowth, and neurodegeneration (Berridge, 1998; Ciccolini et al., 2003).”
Stradecki, H. M., Cohan, C. H., Raval, A. P., Dave, K. R., Reginensi, D., Gittens, R. A., Youbi, M., & Pérez‐Pinzón, M. A. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170057 · Cited by 23 · see citing works
“…an over-activation of the CA3 cells during ischemia and reperfusion caused the changes in CA1 morphology as calcium influx through NMDA receptors is necessary for dendritic outgrowth [119–121] and excessive dendritic outgrowth has been observed in states of over-activation such as epilepsy [122].”
Mizuno, K., Kurokawa, K., & Ohkuma, S. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.03.036 · Cited by 18 · see citing works
“Increased intracellular calcium concentration is a key factor to initiate and regulate a wide range of neuronal functions including neurotransmitter release, synaptic plasticity, neurite outgrowth, and neurodegeneration (Berridge, 1998; Ciccolini et al., 2003).”
Sun, C., Shao, J., Su, L., Zhao, J., Bi, J.-Z., Yang, S.-N., Zhang, S. L., Gao, J., & Miao, J. (2013) · Cell Transplantation · doi:10.3727/096368912x657413 · Cited by 18
Rubini, P., Milošević, J., Engelhardt, J., Al-Khrasani, M., Franke, H., Heinrich, A., Sperlágh, B., Schwarz, S., Schwarz, J., Nörenberg, W., et al. (2009) · Cell Calcium · doi:10.1016/j.ceca.2009.03.008 · Cited by 18
Deng, L.-X., Ruan, Y.-W., Chen, C., Frye, C., Xiong, W., Jin, X.-M., Jones, K., Sengelaub, D., & Xu, X.-M. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.12.018 · Cited by 17 · see citing works
“Activation of NMDA receptors stimulates dendritic outgrowth by increasing intracellular calcium (Cambray-Deakin and Burgoyne, 1992; Ciccolini et al., 2003; Hirai and Launey, 2000).”
BackgroundMizuno, K., Kurokawa, K., & Ohkuma, S. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07827.x · Cited by 17 · see citing works
“Calcium is a ubiquitous intracellular signaling molecule required for initiating and regulating a wide variety of neuronal functions including neurotransmitter release, synaptic plasticity, neurite outgrowth, and neurodegeneration (Berridge 1998; Ciccolini et al. 2003).”
BackgroundCoincidence detection enhances appropriate wiring of the nervous system.
Spitzer, N. (2004) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0401270101 · Cited by 17 · see citing works
Redondo, C., Lopez-Toledano, M., Lobo, M. T., Gonzalo-Gobernado, R., Reimers, D., Herranz, A., Paíno, C., & Bazán, E. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21245 · Cited by 16 · see citing works
“In fact, Ca is a key regulator of multiple cellular processes, including neurite outgrowth in neurospherederived precursors (Ciccolini et al., 2003) and hypertrophy of astrocytes (Schubert et al.”
BackgroundInfluentialRebellato, P., Kaczyńska, D., Kanatani, S., Rayyes, I. A., Zhang, S., Villaescusa, C., Falk, A., Arenas, E., Hermanson, O., Louhivuori, L. M., et al. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.01.015 · Cited by 17 · see citing works
Liljelund, P., Ferguson, C., Homanics, G., & Olsen, R. (2005) · Epilepsy Research · doi:10.1016/j.eplepsyres.2005.07.005 · Cited by 13
Use of calcium channel blockers after stroke is not associated with poor outcome
Dowlatshahi, D., Fang, J., Kawaja, M., & Hakim, A. (2006) · Journal of Neurology · doi:10.1007/s00415-006-0249-1 · Cited by 12
“More recent data suggest that neurite outgrowth requires activation of the calcium channels [3].”
BackgroundSamarasinghe, R. A., Kanuparthi, P. S., Greenamyre, J., DeFranco, D., & Maio, R. D. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.06.020 · Cited by 11 · see citing works
Shao, J., Sun, C., Su, L., Zhao, J., Zhang, S. L., & Miao, J. (2012) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2012.09.013 · Cited by 11
“Ca2+ imaging experiments were performed as described by Ciccolini et al. (2003). In brief, after loaded with 2 M Fluo3 plus pluronic F127 (Invitrogen, USA) for 30 min in an extracellular medium (EM) containing (in mM): 140 NaCl, 3 KCl, 1 MgCl2, 2 CaCl2, 10 HEPES, 10 glucose, the cells were monitored by using a laser s…”
MethodGakhar‐Koppole, N., Bengtson, C., Parlato, R., Horsch, K., Eckstein, V., & Ciccolini, F. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.06020.x · Cited by 11 · see citing works
“entiation, and that membrane depolarization with HiK increases the frequency of Ca signals, the number of cells displaying Ca transients and the number of neurons expressing GABA (Ciccolini et al., 2003).”
BackgroundInfluentialSelf-citationGafarov, F. (2006) · Journal of Integrative Neuroscience · doi:10.1142/s0219635206001136 · Cited by 11
“In this paper, we propose a new theoretical approach for description of activity-dependent evolution and self-wiring between binary neurons.”
BackgroundAltering the fate of stem cells from midgut of Heliothis virescens:the effect of calcium ions.
Loeb, M. (2005) · Archives of Insect Biochemistry and Physiology · doi:10.1002/arch.20060 · Cited by 11
Glyphosate‐based herbicide induces long‐lasting impairment in neuronal and glial differentiation
Reis, L. T. C., Raciti, M., Rodriguez, P. G., Joseph, B., Rayyes, I. A., Uhlén, P., Falk, A., Lima, S. T. D. C., & Ceccatelli, S. (2022) · Environmental Toxicology · doi:10.1002/tox.23549 · Cited by 9 · see citing works
Haijima, A., Lesmana, R., Shimokawa, N., Amano, I., Takatsuru, Y., & Koibuchi, N. (2017) · The Journal of Toxicological Sciences · doi:10.2131/jts.42.407 · Cited by 13 · see citing works
“Intracellular Ca2+ plays important roles in various neurodevelopmental processes including cell proliferation, differentiation, dendritic spine growth, synaptic plasticity and neurotransmission (Berridge et al., 2000; Ciccolini et al., 2003).”
Trinh, H.-H., Reid, J., Shin, E., Liapi, A., Parnavelas, J., & Nadarajah, B. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05194.x · Cited by 8 · see citing works
“Further, experimentally induced changes in the frequency of Ca2+ transients have been correlated with the onset of GABAergic phenotype in neural precursors (Ciccolini et al., 2003; for review, see Spitzer et al., 2004).”
BackgroundRac1, Rac3 GTPases and TPC2 are required for axonal outgrowth and migration of cortical interneuronsPreprint
Kounoupa, Z., Tivodar, S., Theodorakis, K., Kyriakis, D., Denaxa, M., & Karagogeos, D. (2022) · bioRxiv · doi:10.1101/2022.11.07.515393 · Cited by 7 · see citing works
“Spontaneous Ca+2 signaling was identified as an intrinsic characteristic of differentiating neurosphere precursors derived from embryonic striatal cells (Ciccolini et al., 2003).”
BackgroundMizuno, K., Kurokawa, K., & Ohkuma, S. (2014) · Journal of Neuroscience Research · doi:10.1002/jnr.23518 · Cited by 6 · see citing works
Su, L., Zhao, J., Zhao, B.-X., Zhang, S. L., & Miao, J.-Y. (2011) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2011.07.002 · Cited by 7
Nair, S., Agrawal, N., & Hasan, G. (2007) · Invertebrate Neuroscience · doi:10.1007/s10158-007-0048-0 · Cited by 7 · see citing works
“Recent work from ex vivo studies in Xenopus and mouse has shown that neurotransmitters and their cognate receptors as well as neurite growth and branching are specified by patterns of spontaneous electrical activity, measured as the frequency of Ca-spikes and global Ca transients, in developing networks (Borodinsky et…”
BackgroundPaudel, S., Ablondi, E. F., Sehdev, M., Marken, J. P., Halleran, A. D., Rahman, A., Kemper, P., & Saha, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081880 · Cited by 6
“Different groups have defined a spike as: (i) an instance of fluorescence intensity greater than 150% of the baseline (dF/F0) [34]; (ii) a transient amplitude with a rise time of 5 s reaching more than 20% of the baseline value (dF/F0) as determined by the values over the previous 10 min [39]; (iii) a transient amplit…”
Background
- 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
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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