UC Davis

Cellular migration is essential for an assortment of developmental processes ranging from embryogenesis to neurodevelopment. Oftentimes, cellular migration through narrow spaces is limited by nuclear migration,such as is the case for cancer metastasis and in immune response (i.e. white blood cells rushing to the site of injury). Nuclear migration through small constrictions has been studied in vitro but not in vivo. Here, we look at nuclear migration in the context of the developing vulval and neural precursors of Caenorhabditis elegans. During the mid-L1 larval stage, six pairs of P-cell nuclei migrate from the lateral half of the worm to the ventral cord, where they will divide and progress into the vulval and neural precursor cells. These nuclei must migrate through a constriction between the cuticle and the muscle of the developing animal that is about 5% of the diameter of nucleus in the early L1 stage. We explore the mechanisms which allow them to stably migrate in this normal developmental process. Typically, this process has been facilitated by the microtubule-based SUN-KASH pathway, which serve as the tracks for the migrating nuclei. Previous studies have shown that in the absence of the SUN-KASH pathway, these nuclei still migrate at 15°C. We found that there is an actin-based pathway which aids the migration process at 15°C in parallel and in absence of the SUN-KASH pathway. We hypothesized that FLN-2, a filamin, crosslinks branched actin networks and organized actin bundles to support stable nuclear migration through narrow spaces. We found that in the absence of unc-84 (a SUN protein) and/or fln-2, that nuclear rupture events were more prevalent in the migrating P cells, while the absence of unc-84 resulted in the formation of micronuclei in the early and mid-migration stages. We propose future work to determine how FLN-2 may be facilitating P-cell nuclear migration, along with its relationship to UNC-84, LMN-1 (lamin), and CGEF-1 (Cdc42 guanine exchange factor).