Oligodendrocyte precursor cells ingest axons in the mouse neocortex
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 23, 2022
- Source ID
- 10.1073/pnas.2202580119
Entities
People
- Adam A. Bleckert
- Agnes L. Bodor
- Aleksandar Zlateski
- Alyssa M. Wilson
- Carolyn M. Ott
- Casey M Schneider-Mizell
- Chris S. Jordan
- Daniel J. Bumbarger
- Derrick Brittain
- Dodam Ih
- Dwight E. Bergles
- Ed S Lein
- Forrest Collman
- Gayathri Mahalingam
- H. Sebastian Seung
- Ignacio Tartavull
- Jenna C Glatzer
- Jennifer Lippincott-Schwartz
- Jingpeng Wu
- JoAnn Buchanan
- Jonathan Zung
- Kisuk Lee
- Leila Elabbady
- Manuel Castro
- Marc Takeno
- Nicholas L. Turner
- Nico Kemnitz
- Nikolas L. Jorstad
- Nuno Macarico da Costa
- R Clay Reid
- Ran Lu
- Rebecca D Hodge
- Russel M Torres
- Sergiy Popovych
- Shang Mu
- Sharmishtaa Seshamani
- Sven Dorkenwald
- Thomas Macrina
- Trygve E. Bakken
- Wenjing Yin
- William Silversmith
- William Wong
Organizations
- Howard Hughes Medical Institute
- Intelligence Advanced Research Projects Activity
- Johns Hopkins University
- National Institute of Neurological Disorders and Stroke
- National Institutes of Health
- Princeton University