Electron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids.

Hoffmann, Patrick C; Giandomenico, Stefano L; Ganeva, Iva; Wozny, Michael R; Sutcliffe, Magdalena; Lancaster, Madeline A; Kukulski, Wanda (2021). Electron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids. eLife, 10 eLife Sciences Publications 10.7554/eLife.70269

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Ganeva, Iva and Kukulski, Wanda

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2050-084X

Publisher:

eLife Sciences Publications

Language:

English

Submitter:

Barbara Franziska Järmann-Bangerter

Date Deposited:

02 Dec 2021 10:49

Last Modified:

02 Dec 2021 10:49

Publisher DOI:

10.7554/eLife.70269

PubMed ID:

34698018

Uncontrolled Keywords:

CLEM axons cell biology cerebral organoids cryo-EM cryo-ET human

BORIS DOI:

10.48350/161699

URI:

https://boris.unibe.ch/id/eprint/161699

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