PT  - JOURNAL ARTICLE
AU  - Patrick C. Hoffmann
AU  - Stefano L. Giandomenico
AU  - Iva Ganeva
AU  - Michael R. Wozny
AU  - Magdalena Sutcliffe
AU  - Wanda Kukulski
AU  - Madeline A. Lancaster
TI  - The supramolecular landscape of growing human axons
AID  - 10.1101/2020.07.23.216622
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.23.216622
4099  - http://biorxiv.org/content/early/2020/07/23/2020.07.23.216622.short
4100  - http://biorxiv.org/content/early/2020/07/23/2020.07.23.216622.full
AB  - During brain development, human 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 inaccessible to imaging at molecular resolution in a near-native context. Here we apply cryo-correlative light microscopy and electron tomography to growing axonal tracts from human cerebral organoids. 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 data provide an unprecedented resource and reveal a molecular architecture that helps explain the unique biology of growing human axons.Competing Interest StatementThe authors have declared no competing interest.