Apaf-1-independent programmed cell death in mouse development

Akiomi Nagasaka, K. Kawane, H. Yoshida, S. Nagata

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Many cells die during mammalian development and are engulfed by macrophages. In DNase II -/- embryos, the TUNEL-positive DNA of apoptotic cells is left undigested in macrophages, providing a system for studying programmed cell death during mouse development. Here, we showed that an Apaf-1-null mutation in the DNase II -/- embryos greatly reduced the number of macrophages carrying DNA at E11.5. However, at later stages of the embryogenesis, a significant number of macrophages carrying undigested DNA were present in Apaf-1 -/- embryos, indicating that cells died and were engulfed in an Apaf-1-independent manner. In most tissues of the Apaf-1 -/- embryos, no processed caspase-3 was detected, and the DNA of dead cells accumulated in the macrophages appeared intact. Many nonapoptotic dead cells were found in the tail of the Apaf-1 -/- embryos, suggesting that the Apaf-1-independent programmed cell death occurred, and these dead cells were engulfed by macrophages. In contrast, active caspase-3 was detected in E14.5 thymus of Apaf-1 -/- embryos. Treatment of fetal thymocytes with staurosporine, but not etoposide, induced processing of procaspases 3 and 9, indicating that the E14.5 thymocytes have the ability to undergo caspase-dependent apoptosis in an Apaf-1-independent manner. Thus, programmed cell death in mouse development, which normally proceeds in an efficient Apaf-1-depenent mechanism, appears to be backed up by Apaf-1-independent death systems.

Original languageEnglish
Pages (from-to)931-941
Number of pages11
JournalCell Death and Differentiation
Volume17
Issue number6
DOIs
Publication statusPublished - Jun 1 2010
Externally publishedYes

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Cell Death
Embryonic Structures
Macrophages
Caspase 3
Deoxyribonucleases
DNA
Thymocytes
Staurosporine
Caspase 9
In Situ Nick-End Labeling
Etoposide
Caspases
Thymus Gland
Embryonic Development
Tail
Apoptosis
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Apaf-1-independent programmed cell death in mouse development. / Nagasaka, Akiomi; Kawane, K.; Yoshida, H.; Nagata, S.

In: Cell Death and Differentiation, Vol. 17, No. 6, 01.06.2010, p. 931-941.

Research output: Contribution to journalArticle

Nagasaka, Akiomi ; Kawane, K. ; Yoshida, H. ; Nagata, S. / Apaf-1-independent programmed cell death in mouse development. In: Cell Death and Differentiation. 2010 ; Vol. 17, No. 6. pp. 931-941.
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