TARGET FACULTY/NOVEL EXTRACELLULAR PROTEINS IN AXON GUIDANCE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The cells of our nervous system are separated by large distances and have to be connected to one another by wiring capable of carrying electrical or chemical signals. The individual fibers of the wiring are known as axons, and in the early embryo they have to navigate large distances to connect up the nervous system. Understanding what are the landmarks they use to navigate is of great interest, not only for understanding how our brains form, but also as a starting point to devise ways to stimulate the re-growth of axons after injury, especially spinal cord injuries. Very few navigational cues are currently known, certainly not enough to explain the complexity of connections in our brains. This subproject is focused on trying to identify novel cues and novel receptors that the axons use to sense the cues. We use the fruit fly as a model organism as it has very well developed genetics ¿ we can knock out the function of single genes and look to see if navigational errors are made. We identified a set of mutations in single genes that we are particularly interested in, and have found that some of these mutations specifically affect the wiring pattern of the embryonic nervous system. By analyzing in great detail the effect of the mutations on single axons, we believe we have found a protein that growing axons find attractive, so grow towards its source. We also believe we have found the receptor that the axon senses the protein with. We are currently testing these models using tissue culture cells. If our model is correct, the combination of genetic and test tube (in vitro) evidence will shed light on how our spinal cords and brains form, and potentially opens a new avenue for the development of therapies.