Axon guidance in the zebrafish visual system: Analysis of Esrom Mutant

Abstract

This study involves the identification and characterization of the esrom gene. Analysis of zebrafish mutant esrom shows that it is required for axon fasciculation, targeting, branching and skin pigmentation. In the visual system esrom is necessary for the formation of topographic map along the A-P and D-V axis, correct innervation of the pretectal targets and axon bundling in the optic tract. The gene function is required in the eye for retinal ganglion cell (RGC) targeting. Using positional cloning esrom was found to be an orthologue of PAM/Hiw/RPM-1. This large multidomain protein has an E3 ligase activity. Esrom is ubiquitously expressed in the embryo. RGCs require it for proper activation of p38 signal transduction pathway in response to lysophosphatydic acid (LPA). Esrom is also known to regulate phosphorylated tuberin within the growth cones. These data suggest that esrom might act as a molecular switch to integrate signal transduction events in axons.