Epigenetic Interactions and Gene Expression in Peri-Implantation Mouse Embryo Development.
Year: 1993
Type: article
Abstract: One of the central questions in vertebrate developmental biology is how genetic and epigenetic information interact to form a three-dimensional embryo. Previous studies have established the general mechanisms of this process [Edelman, 1988, 1992; Nieuwkoop et al., 1985]: 1) The expression of certain developmentally important genes is regulated epigenetically and is position dependent. This expression depends on previously formed structures and is important for the subsequent interactions leading to the final pattern of the embryo. 2) The impetus for morphogenesis is cellular in origin, because it involves cell division, cell movement, cell adhesion, and cell death. In general, isolated molecular systems are not sufficient to provide the basis for patterning. 3) Cellular forces are linked to the nucleus via molecules such as proteins, peptide growth factors, hormones, receptors, and intracellular signal transduction cascades. The major tasks remaining for a resolution of this central question are to identify the specific gene products and control loops that link the tissue, cellular, and molecular levels of embryonic regulation.
The early morphogenesis of mammalian embryos emphasizes the differentiation of cell types that are essential for early embryonic nutrition within the maternal reproductive tract. Thus preimplantation development of eutherian embryos consists essentially of forming an outer layer of cells (trophectoderm) that is involved in attachment to the uterus [reviewed by Cruz and Pedersen, 1991]. Marsupial embryos also form an outer layer of cells (protoderm), but it is less invasive than the trophectoderm layer of eutherian embryos and generally does not develop into a chorioallantoic placenta [reviewed by Selwood, 1992]. Instead, marsupial embryos derive their nutrition through a vascularized yolk sac that becomes closely apposed to the uterine walls. Eutherian mammals, especially rodents, also utilize the yolk sac for early nutrition, before the chorioallantoic placenta is fully functional [Perry, 1981]. Thus mammals become equipped during their peri-implantation development for growth within the maternal uterine environment. By contrast, oviparous vertebrates are provisioned with nutritional resources by the yolk contained within the egg and proceed directly from cleavage to morphogenesis of the embryo proper.
Despite these differences in their strategies for embryonic nutrition, all vertebrates share the same basic body plan, i.e., they are bilaterally symmetrical quadripeds and might be expected to have similar embryonic strategies for achieving this form. Mechanisms involved in vertebrate body pattern formation are particularly evident during gastrulation, when mesoderm cells initially appear between ectoderm and endoderm layers at the prospective posterior end of the embryo, thus generating its anteroposterior axis. After gastrulation, neurulation occurs as the result of inductive interactions between mesoderm and the overlying ectoderm [Spemann, 1938; Cooke, 1985; Hamburger, 1988; Jones and Woodland, 1989]. Other dorsal mesoderm eventually forms the future notochord and somites, while ectoderm and endoderm develop into axial structures of the nervous system and the gut, respectively. The mesoderm becomes further subdivided as it moves toward the prospective head, trunk, and tail regions and mediates the specification of regional tissue identities as the anteroposterior structures are formed in the adjacent neural plate and endoderm. Morphogenetic mechanisms during this period of vertebrate development have been studied mainly in amphibian and bird embryos [Keller et al., 1992].
While these extensive experimental studies of morphogenetic mechanisms in other vertebrate classes have provided an understanding of the importance of epigenetic interactions in early development, relatively little is known about the cellular or molecular bases for these processes in mammals. This is due in part to the difficulty in obtaining sufficient amounts of preimplantation or peri-implantation material for biochemical or molecular analysis. However, the application of in situ hybridization and polymerase chain reaction (PCR) technologies has facilitated the analysis of gene expression at these early stages of development [Wilkinson and Green, 1990; Rappolee et al., 1989]. Although analysis of mammalian development in vitro remains more cumbersome than that of amphibian or bird embryo systems, model cell systems have been developed for studying the differentiation of early cell lineages: These pluripotent cell types include both embryonal carcinoma (EC) cell lines and embryonic stem (ES) cell lines [Robertson, 1987]. Moreover, studies involving gene targeting and homologous recombination in ES cells are being used to produce genetically altered mice, thus providing a powerful approach for determining the role of specific molecules in mammalian development [Rossant and Joyner, 1989; Rossant and Hopkins, 1992].
In view of these advances in the field of mammalian developmental biology, we have undertaken a review of the role of epigenetic interactions in the differentiation of the extraembryonic and embryonic cell lineages that constitute the peri-implantation mouse embryo. In the first section, we review the differentiation and fate of the cell lineages that form during preimplantation mouse development (trophectoderm [TE], inner cell mass [ICM], and primitive endoderm and primitive ectoderm), emphasizing the evidence for epigenetic interactions in their development; we also consider the implications for epigenetic interactions of studies of model cell systems, EC and ES cells, and from genomic imprinting. In the second section we summarize observations of some potential epigenetic signalling molecules, or morphogens, that have been identified in mouse embryos, and we also consider the role of transcription factors that could be responsible for the influence of epigenetic signals on lineage-specific gene expression. Although evidence about the function of specific molecules in these early morphogenetic events is limited, we cite a combination of in vivo and in vitro studies to summarize the role of epigenetic interactions in mouse embryogenesis.
Source: PubMed
Authors: Jean J Latimer, Roger A Pedersen
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2417383583