Oligodendrocyte precursor cells ingest axons in the mouse neocortex

Jo Ann Buchanan, Leila Elabbady, Forrest Collman, Nikolas L. Jorstad, Trygve E. Bakken, Carolyn Ott, Jenna Glatzer, Adam A. Bleckert, Agnes L. Bodor, Derrick Brittain, Daniel J. Bumbarger, Gayathri Mahalingam, Sharmishtaa Seshamani, Casey Schneider-Mizell, Marc M. Takeno, Russel Torres, Wenjing Yin, Rebecca D. Hodge, Manuel Castro, Sven DorkenwaldDodam Ih, Chris S. Jordan, Nico Kemnitz, Kisuk Lee, Ran Lu, Thomas Macrina, Shang Mu, Sergiy Popovych, William M. Silversmith, Ignacio Tartavull, Nicholas L. Turner, Alyssa M. Wilson, William Wong, Jingpeng Wu, Aleksandar Zlateski, Jonathan Zung, Jennifer Lippincott-Schwartz, Ed S. Lein, H. Sebastian Seung, Dwight E. Bergles, R. Clay Reid, Nuno Maçarico da Costa

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This physical transformation of neurons is facilitated by the engulfment and degradation of axonal branches and synapses by surrounding glial cells, including microglia and astrocytes. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia have made it difficult to define the contribution of these and other glial cell types to this crucial process. Here, we used large-scale, serial section transmission electron microscopy (TEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex, providing unprecedented resolution of their morphology and composition. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors, frequently surrounded small branches of axons. Numerous phagosomes and phagolysosomes (PLs) containing fragments of axons and vesicular structures were present inside their processes, suggesting that OPCs engage in axon pruning. Single-nucleus RNA sequencing from the developing mouse cortex revealed that OPCs express key phagocytic genes at this stage, as well as neuronal transcripts, consistent with active axon engulfment. Although microglia are thought to be responsible for the majority of synaptic pruning and structural refinement, PLs were ten times more abundant in OPCs than in microglia at this stage, and these structures were markedly less abundant in newly generated oligodendrocytes, suggesting that OPCs contribute substantially to the refinement of neuronal circuits during cortical development.

Original languageEnglish (US)
Article numbere2202580119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number48
DOIs
StatePublished - Nov 29 2022

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • axonal pruning
  • engulfment
  • oligodendrocyte precursor cells
  • phagolysosomes

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