When a eukaryotic cell divides the duplicated chromatin has to be precisely segregated and enclosed by a new nuclear envelope (NE). Failure in these key processes results in dramatic alterations of gene expression and genome instability. To identify and characterize components that regulate mitosis, focusing mainly on NE formation, we study early embryogenesis in the nematode Caenorhabditis elegans. Due to its well-characterized and rapid embryogenesis C. elegans provides a powerful model system for the analysis of mitotic events. In addition, depletion of gene products by RNA interference (RNAi) is extremely efficient in the nematode and allows evaluation of gene function also on a whole-organism scale.

 

The NE consists of three major components: the nuclear membranes, the nuclear pore complexes (NPCs), and the nuclear lamina. NPCs are composed of multiple copies of approximately 30 different nucleoporins and regulate transport between the cytoplasm and the nucleus. Through a systematic depletion of nucleoporins we have discovered that several of these proteins in addition to their roles in transport are essential for reforming the NE after mitosis. Moreover, we have recently identified a novel essential NE protein called MEL-28 that localizes to NPCs in interphase and to chromatin during mitosis. MEL-28 regulates NE and NPC formation in a manner conserved from nematodes to vertebrates. We are currently analyzing the specific defects caused upon depletion of other NE proteins combining advanced light microscopy, genome-wide RNAi and biochemical approaches.

In addition to analyzing the activities of NE proteins during cell division we have recently started to study their role more broadly during animal development. In particular, we have identified a novel NE protein essential for maintaining the integrity of the gonad and for proper vulva formation, implying NE proteins in several important signaling pathways.