A Critical Role for the Fascin Family of Actin Bundling Proteins in Axon Development, Brain Wiring and Function

Actin-based cell motility drives many neurodevelopmental events including guided axonal growth. Fascin is a major family of F-actin bundling proteins, but its role in axon development and brain wiring is unknown. Here, we report that fascin is required for axon development, brain wiring and function. We show that fascin is enriched in the motile filopodia of axonal growth cones and its inhibition impairs axonal extension and branching of hippocampal neurons in culture. We next provide evidence that fascin is essential for axon development and brain wiring using Drosophila melanogaster as an in vivo model. Drosophila express a single ortholog of mammalian fascin called Singed (SN), which is highly expressed in the mushroom body (MB) of the central nervous system. We observe that loss of SN results in drastic MB disruption, highlighted by α- and β-lobe defects that are consistent with altered axonal guidance. SN-null flies also exhibit defective sensorimotor behaviors as assessed by the negative geotaxis assay. MB-specific expression of SN in SN-null flies rescues MB structure and sensorimotor deficits, indicating that SN functions autonomously in MB neurons. Together, our data from primary neuronal culture and in vivo models highlight a critical role for fascin in brain development and function.