Activity-dependent mechanisms regulate multiple aspects of visual system development. One way that activity can influence the development of neuronal connections is by the induction of activity-regulated or """"""""candidate plasticity"""""""" genes (CPGs). The protein products of these genes may then affect the morphological development of neurons and the formation of synaptic connections. We propose to study the function of two activity-regulated genes, homer and cpgl5, in the development of the visual system of the frog, Xenopus. We do this by expressing either wild type or mutant genes in the optic tectum, combined with in vivo time-lapse confocal imaging and electrophysiological studies of retinotectal connectivity. CPG15 enhances the morphological development of tectal cell dendrites and retinal axons and it promotes the development of retinotectal synaptic connections. We now propose to determine the mechanisms that regulate the expression, trafficking and function of endogenous CPG15. Our studies on Homer are also quite exciting. Xenopus has 2 Homer isoforms, one (Homer la) is induced by activity and the other (Homer 1b) is not. Homer 1b is a cytosolic anchoring protein that is thought to link cell surface receptors to intracellular calcium stores. Our studies suggest that Homer 1b is required for axon guidance in optic tectal neurons. We propose to test the hypothesis that Homer 1b regulates calcium signaling in growth cones in response to axon guidance cues in the environment. We will determine the generality of the role of Homer 1b in axon guidance by testing its function in tectal cell axons and retinal ganglion cell axons. The Xenopus visual system is ideal for these experiments because one can collect images of the developing visual system under control or experimentally altered conditions. We will continue to use our expertise in in vivo imaging of neuronal morphology and intracellular calcium dynamics. The addition of two-photon laser scanning imaging to our imaging repertoire has significantly increased our ability to resolve detailed structural dynamics deep in the brain and over a wide range of time scales not permitted by traditional confocal microscopy. We will apply these powerful approaches to test the function of activity-regulated genes in the development of visual system connectivity.
| Foa, Lisa; Jensen, Kendall; Rajan, Indrani et al. (2005) Homer expression in the Xenopus tadpole nervous system. J Comp Neurol 487:42-53 |
