Electron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids.
Authors
Publication Date
2021-10-26Journal Title
Elife
ISSN
2050-084X
Publisher
eLife Sciences Publications, Ltd
Volume
10
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Hoffmann, P. C., Giandomenico, S. L., Ganeva, I., Wozny, M. R., Sutcliffe, M., Lancaster, M. A., & Kukulski, W. (2021). Electron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids.. Elife, 10 https://doi.org/10.7554/eLife.70269
Description
Funder: Natural Sciences and Engineering Research Council of Canada; FundRef: http://dx.doi.org/10.13039/501100000038
Abstract
During brain development, axons must extend over great distances in a relatively short amount of time. How the subcellular architecture of the growing axon sustains the requirements for such rapid build-up of cellular constituents has remained elusive. Human axons have been particularly poorly accessible to imaging at high resolution in a near-native context. Here, we present a method that combines cryo-correlative light microscopy and electron tomography with human cerebral organoid technology to visualize growing axon tracts. Our data reveal a wealth of structural details on the arrangement of macromolecules, cytoskeletal components, and organelles in elongating axon shafts. In particular, the intricate shape of the endoplasmic reticulum is consistent with its role in fulfilling the high demand for lipid biosynthesis to support growth. Furthermore, the scarcity of ribosomes within the growing shaft suggests limited translational competence during expansion of this compartment. These findings establish our approach as a powerful resource for investigating the ultrastructure of defined neuronal compartments.
Keywords
Tools and Resources, Cell Biology, cryo-EM, CLEM, cerebral organoids, cryo-ET, axons, Human
Sponsorship
Medical Research Council (MC_UP_1201/9)
European Research Council (ERC STG 757710)
Medical Research Council (MC_UP_1201/8)
Identifiers
70269
External DOI: https://doi.org/10.7554/eLife.70269
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329984
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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