Project Summary
The actin cytoskeleton and its dynamic regulation play an essential role in
neuronal development and function. The proposed study aims to investigate the role of
Fascin, a family of actin bundling proteins, in brain development and function. Fascin1
exhibits an intriguing expression profile in mammalian brains: it is highly expressed
during development but the expression is substantially decreased in the adult brain
During development, elongating axons are guided to their specific targets for synaptic
connections. Axon pathfinding depends on the motile growth cone at the tip of
developing axons, which senses and responds to a variety of extracellular signals to
navigate through a complex and changing environment. The first part of the proposed
study aims to test the hypothesis that fascin, a family of actin filament bundling proteins,
functions in the formation and dynamic regulation of growth cone filopodia during axon
guidance. The part of research will take advantage of our expertise in growth cone
research, and employment of a multifaceted approach involving imaging, molecular
manipulation, and combined assays in cell cultures and ex vivo brain tissues.
While fascin1 expression is substantially reduced in adult brains, fascin1 remains
highly expressed in adult hippocampus. We will test the exciting hypothesis that fascin1
plays an important role in the formation, maintenance, and remodeling of mossy fiber-
CA3 synaptic connections. Using a combination of an in vivo labeling and manipulation,
imaging, and electrophysiology, we aim to evaluate and establish, for the first time, the
role of fascin1 and its actin bundling in brain development and synaptic regulation in
adult brain. Given that elevated fascin1 levels have been associated with cancer cell
metastasis, the proposed work on fascin1 will not only provide significant insights into
the molecular mechanisms of brain development and function, but also extend our
knowledge concerning the actin mechanisms underlying directed cell movement in many
physiological and pathological events.