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Cited by 34Axon Guidance and Neuronal SignalingNeurogenesis and neuroplasticity mechanismsCellular Mechanics and Interactions

Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography

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Atherton, Joseph, Stouffer, Melissa, Francis, Fiona, Moores, Carolyn A.·2022·Journal of Cell Science
DOI 10.1242/jcs.259234PMC PMC9016625

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Abstract

Neurons extend axons to form the complex circuitry of the mature brain. This depends on the coordinated response and continuous remodelling of the microtubule and F-actin networks in the axonal growth cone. Growth cone architecture remains poorly understood at nanoscales. We therefore investigated mouse hippocampal neuron growth cones using cryo-electron tomography to directly visualise their three-dimensional subcellular architecture with molecular detail. Our data showed that the hexagonal arrays of actin bundles that form filopodia penetrate and terminate deep within the growth cone interior. We directly observed the modulation of these and other growth cone actin bundles by alteration of individual F-actin helical structures. Microtubules with blunt, slightly flared or gently curved ends predominated in the growth cone, frequently contained lumenal particles and exhibited lattice defects. Investigation of the effect of absence of doublecortin, a neurodevelopmental cytoskeleton regulator, on growth cone cytoskeleton showed no major anomalies in overall growth cone organisation or in F-actin subpopulations. However, our data suggested that microtubules sustained more structural defects, highlighting the importance of microtubule integrity during growth cone migration.

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  • Several studies have imaged neuronal processes by cryo-EM and cryo-ET, showing neurites are accessible to cryogenic imaging but persistent challenges remain at molecular resolution due to poor contrast and cytoplasmic denseness.

    “Several studies have imaged neuronal processes by cryo-EM and cryo-ET19–25, showing that neurites are accessible to cryogenic imaging, while also revealing persistent challenges in obtaining information at a molecular resolution due to poor contrast and cytoplasmic denseness.”

    From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [23]

    The Results section, “Cryo-ET of primary hippocampal neuron growth cones” (page unavailable), reports imaging vitrified growth cones and clearly visualising the neuron interior, supporting the claim that neuronal processes are accessible to cryogenic imaging. The passages do not attribute persistent difficulty obtaining molecular-resolution information to poor contrast or cytoplasmic denseness; searches for those limitations did not find such a statement. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Atherton, J., Stouffer, M., Francis, F., & Moores, C. A.
Affiliations
  • University of London (GB)
  • Inserm (FR)
Corresponding author
  • Atherton, Joseph
  • Moores, Carolyn A.
ORCID
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2022-04-01
Volume
135
Issue
7
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.259234
PMC
PMC9016625
OpenAlex
W4225822689
Cited by
34
References
0
Citations by year
2026: 5 · 2025: 9 · 2024: 10 · 2023: 4 · 2022: 6
FWCI
3.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cell Science (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • BIROn (Birkbeck, University of London) (acceptedVersion)
  • HAL (submittedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Medical Research Council (MR/R000352/1)
  • Wellcome Trust (079605/Z/06/Z)
  • Biotechnology and Biological Sciences Research Council (BB/L014211/1)
  • Institut National de la Santé et de la Recherche Médicale
  • Centre National de la Recherche Scientifique
  • Sorbonne Université
  • Agence Nationale de la Recherche (ANR-16-CE16-0011-03)
  • Seventh Framework Programme (EU-HEALTH-2013, DESIRE, N° 60253)
  • European Cooperation in Science and Technology (CA16118)
  • Birkbeck College: Birkbeck University of London
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
growth cones, cytoskeleton, microtubules, F-actin, actin bundles, filopodia, doublecortin, hippocampal neurons, axon guidance, cryo-electron tomography
MeSH terms
Actins, Animals, Axons, Cytoskeleton, Microtubules, Neurons, Growth Cones, Mice, Electron Microscope Tomography

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