Nuclear architecture in developmental biology and cell specialisation.

ABSTRACT

Epigenetic changes, including DNA methylation patterns, histone modifications and histone variants, as well as chromatin remodelling play a fundamental role in the regulation of pre- and postimplantation mammalian development. Recent studies have indicated that nuclear architecture provides an additional level of regulation, which needs to be explored in order to understand how a fertilised egg is able to develop into a full organism. Studies of 3D preserved nuclei of IVF preimplantation embryos from different mammalian species, such as mouse, rabbit and cow, have demonstrated that nuclear architecture undergoes major changes during early development. Both similarities and species-specific differences were observed. Nuclear transfer experiments demonstrated changes of nuclear phenotypes, which to some extent reflect changes seen in IVF preimplantation embryos albeit with a different timing compared with IVF embryos. The dynamics of nuclear architecture is further substantiated by major changes during postmitotic terminal cell differentiation. Recent breakthroughs of 3D fluorescence microscopy with resolution beyond the conventional Abbe limit in combination with 3D electron microscopy provide the potential to explore the topography of nuclear structure with unprecedented resolution and detail.