Ca2+-Signaling in Growth Cone Guidance

Rutgers, The State University Of New Jersey-Rbhs-Robert Wood, Piscataway NJ

Investigators

Abstract

Each function of the adult nervous system, from a simple reflex response to a complex behavior, depends on the actions of distinct neuronal circuits. These circuits operate correctly because their component neurons are appropriately connected to each other. Precise wiring of these circuits requires guided growth of nerve fibers to reach the specific targets. Recent studies have identified a variety of molecular cues that provide the "road signs" for growing nerve fibers to navigate through their complex environment, with some of these cues attracting but others repelling growing nerve fibers. It is believed that the tiny, motile tip of each growing nerve fiber, known as the growth cone, is responsible for reading these "road signs" to steer the fiber in the appropriate direction (steering). Dr. Zheng's study aims to elucidate the mechanism by which motile growth cones accurately read direction from these extracellular cues. The research team will specifically focus on the role of intracellular calcium ions (Ca2+) in the growth cone's sensing of direction from diffusible cues. The hypothesis to be tested is that tempo-spatial Ca2+ signals in the growth cone provide the cellular mechanism for encoding of the directional information in the growth cone to initiate appropriate steering responses. Dr. Zheng's research team will use a combination of high-resolution digital imaging and manipulation techniques to examine the tempo-spatial pattern of intracellular Ca2+ signals associated with growth cone steering in response to different guidance cues. Furthermore, the research team will directly generate a similar tempo-spatial pattern of Ca2+ signals in the growth cone using a sophisticated laser-induced photoactivated release method to elucidate the precise role of these Ca2+ signals in guidance. The long-term goal of the study is to understand the molecular and cellular mechanisms that allow nerve growth cones to accurately sense direction in the complex extracellular space for the generation of highly ordered brain architecture.