We are interested in finding the genes that regulate neuronal growth cone behavior, in particular those that protect the growth cone from the effects of environmental stressors, during development of the zebrafish nervous system. Wiring of the nervous system is not an easy task, as the individual growth cones of several billion neurons – at least in the case of humans - must navigate through a complex and changing environment, often to multiple targets. To accomplish this difficult task, growth cones must be able to integrate multiple guidance signals, and in some cases change their responses to individual signals. These signals are ultimately transduced to the actin cytoskeleton, the regulation of which results in appropriately-directed growth. Not surprisingly, even small disruptions in the signaling involved in this process can result in navigational errors. However, multicellular organisms have seemingly evolved robust measures for correcting these errors (see Hutson and Chien, 2001), though the mechanisms are as yet unknown. Given the somewhat delicate balance that must be achieved by growth cones in order to navigate properly, they are surprisingly resistant to environmental stresors such as heat shock (L. Hutson, unpublished results). In other systems, small heat shock proteins (sHSPs), in particular HSP27, are well known for their roles in regulating actin dynamics and protecting cells from the effects heat shock. Because regulation and protection of the actin cytoskeleton are likely to be central to the robustness of growth cones, we are testing whether sHSPs similarly protect growth cones from heat stress.