Understanding the cellular and molecular mechanisms by which the complement factor C9 can control neural crest migration and invasion. (360G-Wellcome-096620_Z_11_A)

Research regarding Neural Crest (NC) migration is important for understanding the development of many organs and systems. Increasing evidence of similarities between NC migration and cancer metastasis have also attached an additional importance to this area of study. Preliminary investigations have suggested a novel role for the complement cascade in early development with the finding that several complement factors (i.e. C3a, C9) are not only expressed in NC but also required for the migration of this tissue. The proposed project aims toinvestigate the cellular and molecular mechanisms by which complement factor C9 controls NC migration and invasion. We will perform high-resolution time-lapse video analysis of NC migration and invasion in vitro and in vivo, comparing control and C9 deficient NC cells. Several candidates will be testedas possible targets of C9 activity such as alterations in cell adhesion, proliferation and apoptosis. Further study will also aim to identify the domain ofC9 important for this function within NC. Collectively these results should allow us to elucidate a completely novel function for complement factor C9 in NC migration and invasion, which could also be relevant for cancer metastasis.