Maternal program of apoptosis activated shortly after midblastula transition by overexpression of S-adenosylmethionine decarboxylase in Xenopus earlyembryos

When we studied polyamine metabolism in Xenopus embryos, we cloned the cDNA for Xenopus S-adenosylmethionine decarboxylase (SAMDC), which converts SAM (S-adenosylmethionine), the methyl donor, into decarboxylated SAM (dcSAM), the aminopropyl donor, and microinjected its in vitro transcribed mRNA int o Xenopus fertilized eggs. We found here that the mRNA injection induces a SAM deficient state in early embryos due to over-function of the overexpres sed SAMDC, which in turn induces inhibition of protein synthesis. Such embr yos developed quite normally until blastula stage, but stopped development at the early gastrula stage, due to induction of massive cell dissociation and cell autolysis, irrespective of the dosage and stage of the mRNA inject ion. We found that the dissociated cells were TUNEL-positive, contained fra gmented nuclei with ladder-forming DNA, and furthermore, rescued completely by coinjection of Bcl-2 mRNA. Thus, overexpression of SAMDC in Xenopus emb ryos appeared to switch on apoptotic program, probably via inhibition of pr otein synthesis. Here, we briefly review our results together with those re ported from other laboratories. After discussing the general importance of this newly discovered apoptotic program, we propose that the maternal progr am of apoptosis serves as a surveillance mechanism to eliminate metabolical ly severely-damaged cells and functions as a 'fail-safe' mechanism for norm al development in Xenopus embryos. (C) 2000 Elsevier Science Inc. All right s reserved.