Oligodendrocyte precursor cells ingest axons in the mouse neocortex.

TitleOligodendrocyte precursor cells ingest axons in the mouse neocortex.
Publication TypeJournal Article
Year of Publication2022
AuthorsBuchanan JA, Elabbady L, Collman F, Jorstad NL, Bakken TE, Ott C, Glatzer J, Bleckert AA, Bodor AL, Brittain D, Bumbarger DJ, Mahalingam G, Seshamani S, Schneider-Mizell C, Takeno MM, Torres R, Yin W, Hodge RD, Castro M, Dorkenwald S, Ih D, Jordan CS, Kemnitz N, Lee K, Lu R, Macrina T, Mu S, Popovych S, Silversmith WM, Tartavull I, Turner NL, Wilson AM, Wong W, Wu J, Zlateski A, Zung J, Lippincott-Schwartz J, Lein ES, H Seung S, Bergles DE, R Reid C, da Costa NMa├žarico
JournalProc Natl Acad Sci U S A
Volume119
Issue48
Paginatione2202580119
Date Published2022 Nov 29
ISSN1091-6490
KeywordsAnimals, Axons, Mice, Neocortex, Neurons, Oligodendrocyte Precursor Cells, Oligodendroglia
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.

DOI10.1073/pnas.2202580119
Alternate JournalProc Natl Acad Sci U S A
PubMed ID36417438
PubMed Central IDPMC9889886
Grant ListRF1 MH128840 / MH / NIMH NIH HHS / United States
U19 NS104648 / NS / NINDS NIH HHS / United States
U01 MH114824 / MH / NIMH NIH HHS / United States
R01 EY027036 / EY / NEI NIH HHS / United States
R01 NS104926 / NS / NINDS NIH HHS / United States
RF1 MH117815 / MH / NIMH NIH HHS / United States
R01 AG072305 / AG / NIA NIH HHS / United States