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TitleElectron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids.
Journal, issue, pagesElife, Vol. 10, Year 2021
Publish dateOct 26, 2021
AuthorsPatrick C Hoffmann / Stefano L Giandomenico / Iva Ganeva / Michael R Wozny / Magdalena Sutcliffe / Madeline A Lancaster / Wanda Kukulski /
PubMed AbstractDuring 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 ...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.
External linksElife / PubMed:34698018 / PubMed Central
MethodsEM (tomography)
Structure data

EMDB-13195:
Cryo-ET of axons from human cerebral organoids, expressing membrane-targeted GFP
Method: EM (tomography)

EMDB-13196:
Cryo-ET of axons from human cerebral organoids, expressing L1CAM-GFP
Method: EM (tomography)

EMDB-13197:
Cryo-ET of axons grown from human cerebral organoids, expressing ESYT1-GFP
Method: EM (tomography)

Source
  • Homo sapiens (human)

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