Nuclear positioning during development: Pushing, pulling and flowing

The positioning of the nucleus, the central organelle of the cell, is an active and regulated process crucially linked to cell cycle, differentiation, migration, and polarity. Alterations in positioning have been correlated with cell and tissue function deficiency and genetic or chemical manipulation of nuclear position is embryonic lethal. Nuclear positioning is a precursor for symmetric or asymmetric cell division which is accompanied by fate determination of the daughter cells. Nuclear positioning also plays a key role during early embryonic developmental stages in insects, such as Drosophila, where hundreds of nuclei divide without cytokinesis and are distributed within the large syncytial embryo at roughly regular spacing. While the cytoskeletal elements and the linker proteins to the nucleus are fairly well characterised, including some of the force generating elements driving nuclear movement, there is considerable uncertainty about the biophysical mechanism of nuclear positioning, while the field is debating different force models. In this review, we highlight the current body of knowledge, discuss cell context dependent models of nuclear positioning, and outline open questions.