Extending the maternal-zygotic effect with genomic imprinting

Maternal effect refers to the genetic phenomenon in which a phenotype in the progeny is caused by a genetic mutation in the maternal genome rather than a mutation of its own. Maternal effect genes are usually involved in the maternal-to-zygotic transition during embryonic development before zygotic genes are turned on. Although it is widely observed in invertebrate organisms, it is not common in vertebrate animals, especially in mammals. Genomic imprinting is an epigenetic phenomenon that is unique to eutherian mammals, marsupials and plants. One characteristic of genomic imprinting is parental origin-specific expression of imprinted genes. The molecular mechanisms underlying genomic imprinting are poorly understood. Mouse Zfp57 is the first example of a mammalian maternal-zygotic effect gene and it exhibits maternal-zygotic embryonic lethality around midgestation when both maternal and zygotic functions of Zfp57 are absent. Loss of Zfp57 also results in loss of differential DNA methylation at multiple imprinted regions. Interestingly, the midgestational embryonic lethality due to loss of both maternal and zygotic functions of Zfp57 occurs much later than the typically observed maternal-zygotic embryonic lethality during the maternal-to-zygotic transition period in early preimplantation embryos. I hypothesize that gradual loss of heritable genomic DNA methylation imprints over many cell divisions could account for this spatial and temporal discrepancy between the causative molecular defect and the observed phenotype in the Zfp57 mutant.