WATCHING NEURONS GROW: GUIDANCE RECEPTORS, SIGNAL TRANSDUCTION MACHINERY AND CYTOSKELETAL REGULATORS AFFECT GROWTH CONE MORPHOLOGY AND DYNAMICS IN C. ELEGANS

Abstract

The growth cone of a developing axon senses and responds to extracellular cues resulting in the migration of the growth cone and thus the axon to the correct target in the nervous system. Growth cones display dynamic, actin-based filopodial and lamellipodial protrusions. While much work has been done on growth cones in vitro and on fully developed axons in vivo, little has been done to study growth cones in vivo as the organism is developing. This work aims to bridge that gap by using C. elegans as a model system to study in vivo growth cone development. We found that many genes important for proper axon guidance exert their activity on the growth cone. We found a series of actin-modulating proteins important for filopodia formation, a guidance cue and its receptors important for polarity and extent of both filopodial and lammelipodial protrusion, and a pathway of signal transduction proteins and cytoskeletal regulators important for limiting the extent of filopodial protrusion. We show that in each of these cases, the proper control of growth cone morphology was important for the final axon pathfinding outcome. This work bridges the gap between in vitro growth cone analysis and in vivo endpoint analysis, showing a link between developmental control over protrusion and correct axon pathfinding and nervous system development.