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dc.contributor.authorHoffmann, Patrick C
dc.contributor.authorGiandomenico, Stefano L
dc.contributor.authorGaneva, Iva
dc.contributor.authorWozny, Michael R
dc.contributor.authorSutcliffe, Magdalena
dc.contributor.authorLancaster, Madeline A
dc.contributor.authorKukulski, Wanda
dc.date.accessioned2021-10-28T08:08:49Z
dc.date.available2021-10-28T08:08:49Z
dc.date.issued2021-10-26
dc.date.submitted2021-05-11
dc.identifier.issn2050-084X
dc.identifier.other70269
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329984
dc.descriptionFunder: Natural Sciences and Engineering Research Council of Canada; FundRef: http://dx.doi.org/10.13039/501100000038
dc.description.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 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.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.subjectTools and Resources
dc.subjectCell Biology
dc.subjectcryo-EM
dc.subjectCLEM
dc.subjectcerebral organoids
dc.subjectcryo-ET
dc.subjectaxons
dc.subjectHuman
dc.titleElectron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids.
dc.typeArticle
dc.date.updated2021-10-28T08:08:46Z
prism.publicationNameElife
prism.volume10
dc.identifier.doi10.17863/CAM.77428
dcterms.dateAccepted2021-10-08
rioxxterms.versionofrecord10.7554/eLife.70269
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Zanetti, Giulia
datacite.contributor.supervisorsenior_editor: Akhmanova, Anna
dc.contributor.orcidHoffmann, Patrick C [0000-0003-3421-6363]
dc.contributor.orcidGiandomenico, Stefano L [0000-0003-4235-8353]
dc.contributor.orcidGaneva, Iva [0000-0003-3221-2502]
dc.contributor.orcidWozny, Michael R [0000-0001-9359-3287]
dc.contributor.orcidSutcliffe, Magdalena [0000-0001-5853-2331]
dc.contributor.orcidLancaster, Madeline A [0000-0003-2324-8853]
dc.contributor.orcidKukulski, Wanda [0000-0002-2778-3936]
dc.identifier.eissn2050-084X
pubs.funder-project-idMedical Research Council (MC_UP_1201/9)
pubs.funder-project-idEuropean Research Council (ERC STG 757710)
pubs.funder-project-idMedical Research Council (MC_UP_1201/8)
cam.issuedOnline2021-10-26


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