The development of the brain is a complex process in which neurons migrate and extend over great distances in order to form functional and precise neural circuits. While many important molecular cues that sculpt the shape of neurons and guide their migratory trajectories have been identified, new molecular cues continue to be discovered and characterized. The purpose of this investigation, conducted by Drs. Barbara Lom and Jennifer Round of Davidson College, is to characterize the functional roles of the Slitrks, a novel family of guidance molecules in the developing nervous system. Slitrk proteins are abundant in the brains of mice and humans; previous studies show that Slitrks can influence neuron shape and trajectory, but further research is needed to understand the role of Slitrks in brain development. Drs. Lom and Round will utilize zebrafish, an appropriate and cost effective animal model for understanding nervous system formation in all vertebrates. Using molecular approaches, they will determine where and when Slitrks are expressed in the zebrafish brain. They will also reduce Slitrk protein levels by using reverse genetic approaches and examine the resulting defects in brain wiring. These experiments will allow Drs. Lom and Round to discover and publish important and novel information on the function of Slitrks in vertebrate brain development. Moreover, the study will be performed at Davidson College, a liberal arts college focused exclusively on undergraduate education. Thus, Drs. Lom and Round will expand our basic knowledge of brain development while simultaneously engaging young students in the scientific research process. This research will provide insight into the molecular basis of nervous system development and provide valuable training for the next generation of scientists.
How the brain is forms and functions is an important question in neuroscience research. We were specifically interested in understanding the molecular cues that guide growing neurons to form proper synapes and networks in teh embryonice brain. The Slitrks are an intriuging family of proteins that have been implicated in early neuronal wiring events. Slitrk genes are present in humans and many other vertebrate species, but how these proteins influence neuronal development is largely unknown. The Slitrks appear something like hybrid molecules, bearing significant resemblance to two distinct and well-studied famiies of molecules, the Slits and the Trks. Both the Slits and the Trks have been widely implicated in imporant events for proper brain development such as neuronal survival and synapttc wiring. Thus far only a few studies have examined Slitrk fucntion in cultured neurons, developing rodents, and human genomes. The zebrafish is a powerful vertebrate model system that provides many advantages for elucidating molecluar function. Through this research project we characterized the expression patterns of Slitrks in the developing zebrafish nervous system, began to determine the function of Slitrk1 in the developing spinal cord, began to identify proteins that interact with Slitrks, and trained undergraduates, a postdoc, and research technicians in modern developmental neurobiology techniques to help train the next generation of scientists.
