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Curr Biol DOI:10.1016/j.cub.2012.03.027

Apoptotic cells are cleared by directional migration and elmo1- dependent macrophage engulfment.

Publication TypeJournal Article
Year of Publication2012
Authorsvan Ham, TJ, Kokel, D, Peterson, RT
JournalCurr Biol
Date Published2012 May 08
KeywordsAdaptor Proteins, Signal Transducing, Apoptosis, Cell Movement, Humans, Macrophages

Apoptotic cell death is essential for development and tissue homeostasis. Failure to clear apoptotic cells can ultimately cause inflammation and autoimmunity. Apoptosis has primarily been studied by staining of fixed tissue sections, and a clear understanding of the behavior of apoptotic cells in living tissue has been elusive. Here, we use a newly developed technique to track apoptotic cells in real time as they emerge and are cleared from the zebrafish brain. We find that apoptotic cells are remarkably motile, frequently migrating several cell diameters to the periphery of living tissues. F-actin remodeling occurs in surrounding cells, but also within the apoptotic cells themselves, suggesting a cell-autonomous component of motility. During the first 2 days of development, engulfment is rare, and most apoptotic cells lyse at the brain periphery. By 3 days postfertilization, most cell corpses are rapidly engulfed by macrophages. This engulfment requires the guanine nucleotide exchange factor elmo1. In elmo1-deficient macrophages, engulfment is rare and may occur through macropinocytosis rather than directed engulfment. These findings suggest that clearance of apoptotic cells in living vertebrates is accomplished by the combined actions of apoptotic cell migration and elmo1-dependent macrophage engulfment.


Alternate JournalCurr. Biol.
PubMed ID22503503
PubMed Central IDPMC3597770
Grant ListU01 NS063733 / NS / NINDS NIH HHS / United States
K01MH091449 / MH / NIMH NIH HHS / United States
K01 MH091449 / MH / NIMH NIH HHS / United States
R01 MH086867 / MH / NIMH NIH HHS / United States
MH086867 / MH / NIMH NIH HHS / United States
NS063733 / NS / NINDS NIH HHS / United States