The establishment of neuronal connectivity requires the growth of axons and their synaptic branches. Following a period of growth, axon extension must be terminated and synaptic branches must be stabilized. The mechanisms that regulate this switch from growth to stability are mostly unexplored. We have identified a signaling pathway that can promote a state of axonal growth by inhibiting axon termination and branch stabilization. Moreover, we have identified a microRNA that can inhibit this pathway, thereby promoting axon termination and branch stabilization. We will use genetic analysis to investigate the role of this microRNA in promoting the switch from axonal growth to stability. MicroRNAs have been associated with many neurodevelopmental disorders. However, the roles that microRNAs play in regulating neuronal development are only beginning to be uncovered. We anticipate that our studies will provide a key example of how microRNAs can control neuronal development and will also identify novel mechanisms that control axon extension and branch formation.
Precise regulation of axon termination and branch stabilization are required for the development of a functional nervous system and disruptions in this process can underlie neurodevelopmental disorders. Thus, the proposed research will lead to the development of fundamental knowledge that could impact the diagnosis and treatment of neurodevelopmental disorders.
| Daniels, Brian P; Snyder, Annelise G; Olsen, Tayla M et al. (2017) RIPK3 Restricts Viral Pathogenesis via Cell Death-Independent Neuroinflammation. Cell 169:301-313.e11 |
