Apoptotic Cells Are Cleared by Directional Migration and elmo1-Dependent Macrophage Engulfment

Tjakko J. van Ham*, David Kokel, Randall T. Peterson

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)

Abstract

Apoptotic cell death is essential for development and tissue homeostasis [1, 2]. Failure to clear apoptotic cells can ultimately cause inflammation and autoimmunity [3, 4]. 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 [5] 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 eimo1-dependent macrophage engulfment.

Original languageEnglish
Pages (from-to)830-836
Number of pages7
JournalCurrent Biology
Volume22
Issue number9
DOIs
Publication statusPublished - 8-May-2012
Externally publishedYes

Keywords

  • IN-VIVO
  • DROSOPHILA EMBRYOGENESIS
  • ZEBRAFISH
  • CLEARANCE
  • DEATH
  • PU.1
  • REQUIREMENT
  • MECHANISM
  • ABLATION
  • RECEPTOR

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