Proper functioning within the nervous system requires neurons to extend axons over long distances to make connections with their target cells (other neurons, muscle etc.). The extension of axons is a dynamic, motile process. Cell surface receptor proteins detect attractive or repulsive cues that guide the axon to its target. Receptors initiate biochemical signaling cascades inside the cell that regulate the motile machinery - essentially actin and myosin interactions. In this proposal, VanBerkum's goal is to identify the signaling pathways used by an axon to regulate myosin activity downstream of both attractive and repulsive signals used to guide an axon at the midline of the developing fruit fly embryo. By using a combination of classic and modern molecular genetic approaches, and assaying axon pathway formation, VanBerkum's lab will build and use several reagents to help identify how three different signaling pathways contribute to the regulation of myosin activity during axon pathway formation. Each of these three signaling pathways are suspected to regulate aspects of motility, and this work focuses on the individual and combined use of these pathways in guiding an axons response to selected cues. Given the universality of these signaling pathways, this work may impact our understanding of several other motile processes during embryonic development, as well as motile processes in adults including for example, immune cell migration toward invading organisms or metastasis of cancer cells.
The broader impact of this project includes the training of several graduate students and participation in outreach programs targeting minority undergraduates and area high school students. VanBerkum also directs the graduate program within his department.
