Gene expression and macromolecular synthesis during preimplantation embryonic development.

The most extensively studied systems of early embryonic development are ones far removed from man and other mammals and include, most notably, the echinoderms and amphibia. Based on work with these and other organisms, there has been built-up an overall picture in which much, if not all, of early post-fertilization development is controlled by messenger RNAs (mRNAs) which are synthesized in the egg but are not activated until after fertilization has occurred (Gross, 1967; Davidson, 1968; Brown and Dawid, 1969; Brachet and Malpoix, 1971). The presence and activity of such masked messenger RNAs (mmRNAs) were originally defined in experiments in which early development was shown to be invulnerable to the effects of actinomycin D, an inhibitor of RNA synthesis. However, the physical existence of these mmRNAs now seems to be firmly established, and it has been possible to isolate and use them to govern protein synthesis in vitro (Gross, et al. 1973; Skoultchi and Gross, 1973). With the development of techniques for the biochemical analysis of the mammalian embryo, it is natural that the question of how early mammalian development is controlled should be of great interest. While the presence or absence of mammalian mmRNAs has not as yet been established, the available information indicates that all stages of preimplantation mammalian development are affected by the genetic activity of the embryo itself. It will be the purpose of this paper to summarize the relevant information obtained principally from our own studies on the preimplantation mouse embryo and, when applicable, from the studies of others with mouse and rabbit embryos. Unless otherwise stated, the material will refer to the developing mouse embryo. between fertilization and implantation. Recent reviews of this subject have been published by Wolf and Engel (1972), Fowler and Edwards (1973), and Biggers and Stern (1973). The evidence will be reviewed in order from the least to the most direct, and the major point to be considered will be the role of embryonic gene action in governing early mammalian development. However, although our emphasis is on genetic control, it is well to keep in mind that gene activity by itself is unlikely to be the whole explanation of development and differentiation. This point was well stated in a recent book by Wright (1973). “Application of the words cause’ or trigger’ to particular components within a differentiating system may delude the user into feeling that there exist certain ‘spontaneous’ or independent factors uniquely capable of causing differentiation to occur. . . . There is no a priori reason for singling out any particular biochemical event on which differentiation depends as being more essential or necessary than others. ... Such an approach renders an objective analysis difficult and stresses the role of components which may or may not be limiting the rate of the differentiation process in question. It appears to be no more justilied or useful to choose selective gene activation as ‘the’ basis of differentiation than to choose, for example, substrate availability.”