Regular Article

Cell Research (2003) 13, 147–158. doi:10.1038/sj.cr.7290159

Overexpression of S-adenosylmethionine decarboxylase (SAMDC) in Xeno-pus embryos activates maternal program of apoptosis as a "fail-safe" mechanism of early embryogenesis

Masatake KAI1, Chikara KAITO1,**, Hiroshi FUKAMACHI1, Takayasu HIGO1,***, Eiji TA-KAYAMA2, Hiroshi HARA3, Yoshikazu OHYA4, Kazuei IGARASHI5 and Koichiro SHIOKAWA1,****

  1. 1Laboratory of Molecular Embryology, Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan
  2. 2Department of Parasitology, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama, 359-8543, Japan
  3. 3Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
  4. 4Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
  5. 5Faculty of Pharmaceutical Sciences, Chiba University, Yayoi-eho 1-33, Inage-ku, Chiba 263-8522, Japan

Correspondence: Dr. Masatake KAI, Department of Anatomy and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, United Kingdom. E-mail: m.kai@ucl.ac.uk

**Laboratory of Developmental Biochemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan

***Department of Basic Medical Sciences, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

****Department of Biosciences, School of Science and Engineering, Teikyo University, Toyosatodai 1-1, Utsunomiya, Tochigi 320-8551, Japan

Received 4 April 2003; Revised 1 May 2003; Accepted 13 May 2003.

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Abstract

In Xenopus, injection of S-adenosylmethionine decarboxylase (SAMDC) mRNA into fertilized eggs or 2-cell stage embryos induces massive cell dissociation and embryo-lysis at the early gastrula stage due to activation of the maternal program of apoptosis. We injected SAMDC mRNA into only one of the animal side blastomeres of embryos at different stages of cleavage, and examined the timing of the onset of the apoptotic reaction. In the injection at 4- and 8-cell stages, a considerable number of embryos developed into tadpoles and in the injection at 16- and 32-cell stages, all the embryos became tadpoles, although tadpoles obtained were sometimes abnormal. However, using GFP as a lineage tracer, we found that descendant cells of the blastomere injected with SAMDC mRNA at 8- to 32-cell stages are confined within the blastocoel at the early gastrula stage and undergo apoptotic cell death within the blastocoel, in spite of the continued development of the injected embryos. These results indicate that cells overexpressed with SAMDC undergo apoptotic cell death consistently at the early gastrula stage, irrespective of the timing of the mRNA injection. We assume that apoptosis is executed in Xenopus early gastrulae as a "fail-safe" mechanism to eliminate physiologically-severely damaged cells to save the rest of the embryo.

Keywords:

SAMDC overexpression, maternal apoptosis program, processing-defective SAMDC mutant, MBT, fail-safe mechanism

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