Turning of nerve growth cones induced by neurotransmitters
Abstract
Pathfinding by growing nerve processes in the developing nervous system depends on the turning response of the growing tip, the growth cone, to extracellular guidance cues. There is evidence in vivo and in cell culture that some growth cones exhibit chemotropic behaviour, but the identity of endogenous chemoattractants remains elusive. Neurotransmitters appear early in the developing embryo and may have morphogenic roles in development. In cell culture a number of neurotransmitters were found to induce growth inhibition or retraction of neurites. Here we report positive turning responses of the nerve growth cone in a defined extracellular gradient of the neurotransmitter acetylcholine (ACh). The growth cone response depends on the activation of neuronal nicotinic ACh receptors, requires the presence of extracellular Ca2+, and appears to be mediated by Ca(2+)-calmodulin-dependent protein kinase II. Fluorescence imaging of cytosolic Ca2+ concentration ([Ca2+]i) at the growth cone showed a small but significant evaluation of [Ca2+]i within minutes of the onset of ACh application and before the turning of the growth cone. These findings suggest that neurotransmitters may serve as specific chemoattractants for growth cone guidance and that cytosolic Ca2+ may act as a second messenger in the cytoplasm of the growth cone to initiate the turning response.
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Even before the cholinergic projections arrive in the cortical areas, the nicotinic and muscarinic receptors are expressed on neural progenitors, playing a role in proliferation/differentiation and axonal guidance events.
“But even before the cholinergic projections arrive in the cortical areas, the nicotinic and muscarinic receptors are expressed on neural progenitors playing a role in proliferation/differentiation and axonal guidance events [214–217].”
From Development of prefrontal cortex (2022) · cites this paper as [217]
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- Authors
- Zheng, J. Q., Felder, M., Connor, J. A., & Poo, M.-M.
- Affiliations
- Columbia University (US)
- Venue
- Nature
- Published
- 1994-03
- Volume
- 368
- Issue
- 6467
- Pages
- 140-144
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2078047724
- Cited by
- 580
- References
- 40
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 11 · 2015: 11 · 2014: 14 · 2013: 17 · 2012: 13
- FWCI
- 16.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM083889)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- growth cone turning, acetylcholine, chemotropism, chemoattractants, neuronal nicotinic acetylcholine receptors, calcium signaling, calcium/calmodulin-dependent protein kinase II, intracellular calcium, neurite guidance, axon guidance
- MeSH terms
- Acetylcholine, Animals, Axons, Calcium, Cell Movement, Cells, Cultured, Chemotactic Factors, Image Processing, Computer-Assisted, Microscopy, Fluorescence, Receptors, Cholinergic, Xenopus, Calcium-Calmodulin-Dependent Protein Kinases, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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