Early mammalian development

Abstract

ABSTRACT Early morphogenesis responds to a biological clock wound up at fertilization. It has been shown, in different biological systems, that cell cleavage per se is not a prerequisite for scheduled tissue-specific enzymes expression (Satoh, 1982) or even for some early morphogenetic events (Lillie, 1902; Kimber and Surani, 1981). On the contrary, a critical DNA replication cycle has been proposed to be responsible for cell commitment during embryogenesis. This hypothesis has been verified for early mouse embryogenesis, using antiproliferative drugs affecting essentially DNA replication. A transient polyamine depletion in early cleaving embryos was shown to induce an early cavitation with regard to the elapsed cell cycles. More recently, we used a more direct way, namely the specific inhibition of DNA polymerase a by aphidicolin: the 4th DNA replication cycle appeared to be the one responsible for the trophectoderm determination. Moreover, trophectodermal cells are able to undergo their typical morphological differentiation in vitro (spreading, outgrowth and nucleus enlargement) in total absence of any additional DNA synthesis from the 32 to 64 cell-blastocyst stage onwards. This total inhibition of DNA replication was achieved by aphidicolin but not by either dideoxythymidine or dideoxythymidine-triphosphate, which is in disagreement with the recent findings of Siegel and Kalf (1982) concerning the involvement of DNA polymerase ft instead of DNA polymerase a in the DNA endoreduplication in giant trophoblast cells. Finally, preliminary experiments also indicate that aphidicolin induces, in F9 teratocarcinoma cells, morphological modifications similar to those recorded at the onset of their retinoic acid-induced differentiation (B. Capone & H. Alexandre).