Engulfment by brain macrophages in a short-lived vertebrate
models exist to study engulfment in the brain and characterize this process during aging and across species. Here we present a genetic model for secretion of a fluorescent protein by neurons in the brain of the African turquoise killifish, the shortest-lived vertebrate that can be bred in captivity. We use this model to identify a population of brain macrophages in the killifish responsible for engulfment of material from the brain extracellular space. Intriguingly, many of these cells bear similarities to mammalian border-associated and monocyte-derived macrophages, rare subsets of macrophages in mouse and human brains noted for their engulfment capabilities. We also find that in our model, killifish brain macrophages decline in engulfment capacity with age. This work highlights how vertebrate brain macrophages, particularly those at brain border regions, can play a critical role in clearance and provides an opportunity to test interventions that can boost engulfment by these macrophages to promote brain resilience in old age and disease.
Authors
- Angela N. Pogson (ORCID: https://orcid.org/0000-0002-6927-2456)
- Jingxun Chen (ORCID: https://orcid.org/0000-0001-7320-8652)
- Philippe Mourrain (ORCID: https://orcid.org/0000-0002-3674-4015)
- Emma K. Costa (ORCID: https://orcid.org/0000-0002-9431-6852)
- Rahul Nagvekar (ORCID: https://orcid.org/0000-0001-8800-7503)
- Ravi D. Nath (ORCID: https://orcid.org/0000-0003-0905-2707)
- Param Priya Singh (ORCID: https://orcid.org/0000-0002-3325-8767)
- B Wang
- Rogelio Barajas
- Paloma Navarro Negredo (ORCID: https://orcid.org/0000-0003-1087-3895)
- James B. Jaggard (ORCID: https://orcid.org/0000-0003-4091-9946)
- Claire N. Bedbrook (ORCID: https://orcid.org/0000-0003-3973-598X)
- Luise A. Seeker (ORCID: https://orcid.org/0000-0001-6375-6372)
- Kristy Red-Horse
- Beth Stevens
- Helena J Barr
- Tony Wyss-Coray (ORCID: https://orcid.org/0000-0001-5893-0831)
- Stephen R. Quake
- Prateek R Kalakuntla
- Anne Brunet
- Azalia M Martínez Jaimes
- Felix Boos
- S V Perry
Institutions
- Broad Institute (US)
- Boston Children's Hospital (US)
- Allen Institute for Brain Science (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- University of California, San Francisco (US)
- Neurosciences Institute (US)
- California Institute for Regenerative Medicine (US)
- Princeton University (US)
- École Polytechnique Fédérale de Lausanne (CH)
- University of St. Francis (US)
- Stanford University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-29
- DOI
- https://doi.org/10.64898/2026.04.28.721434
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Glenn Foundation for Medical Research
- Fondation pour la Recherche Médicale
- NOMIS Stiftung
- National Institutes of Health
- National Center for Research Resources