Genome Imprinting and Development in the Mouse

Development in mammals is influenced by genome imprinting which results in differences in the expression of some homologous maternal and paternal alleles. This process, initiated in the germline, can continue following fertilization with interactions between oocyte cytoplasmic factors and the parental genomes involving modifier genes. Further epigenetic modifications may follow to render the 'imprints' heritable through subsequent cell divisions during development. Imprinting of genes can be critical for their dosage affecting embryonic growth, cell proliferation and differentiation. The cumulative effects of all the imprinted genes are observed in androgenones (AG) and parthenogenones (PG), which reveal complementary phenotypes with respect to embryonic and extraembryonic tissues. The presence of PG cells in chimeras causes growth retardation, while that of AG cells enhanced growth. AG cells apparently have a higher cell proliferation rate and, unlike PG cells, are less prone to selective elimination. However, the PG germ cells are exempt from cell selection. In chimeras, PG cells are more likely to be found in ectodermal derivatives such as epidermis and brain in contrast to AG cells which make pronounced contributions to many mesodermal derivatives such as muscle, kidney, dermis and skeleton. The presence of androgenetic cells in chimeras also results in the disproportionate elongation of the anterior-posterior axis and sometimes in the abnormal development of skeletal elements along the axis. Genetic studies high-light the influence of subsets of imprinted genes, and identify those that are critical for development.