Regulation of growth and differentiation in early development: of mice and models

In this article we describe some of the fundamental processes occurring during early murine development, introduce cellular models used to investigate these processes and review some well-known factors that may be involved in their control. These include transforming growth factor beta, retinoic acid and leukaemia inhibitory factor. Refinements to the culture conditions of embryonic stem and embryonal carcinoma cells have enabled us to test the effects of these factors on growth and differentiation and in particular to establish that their interaction may determine the ultimate developmental state of the cell population. Preliminary studies using neutralizing antibodies in embryos are described that suggest that deregulation of normal expression can lead to a failure to implant. Insights into the events underlying normal embryonic development and implantation, yielded by the type of study described here, may contribute to an understanding of the mechanisms causing early embryonic loss and the role of toxicants in this process.