IBN-9723990 PI: WHEELER The developing nervous system is dependent on many regulatory signals to insure that the different parts of the body will become well integrated with the central nervous system. Neurons that develop in the central nervous system, or in its associated ganglia in the peripheral nervous system, must send out long processes, called axons, that grow into a "target tissue" such as the face, hand or nasal passages. The growth of axons into target tissues is dependent on certain molecular signals that serve as guidance cues. The molecular signals that will be studied in this project, called neurotrophins, foster the growth and survival of growing neurons. Previous research suggests that the availability of neurotrophins, which are made by target tissues, is a factor that determines whether subpopulations of developing neurons survive, and also whether they establish appropriate attachments to their target tissues. The production of neurotrophins by target tissues is limited in both time and quantity, and their concentration is believed to directly influence the successful innervation of designated targets. Dr. Wheeler and her colleagues will investigate the time of expression and the levels of a class of receptor molecules (the "non-catalytic" neurotrophin receptors) that potentially bind and sequester the neurotrophins to prevent axons from becoming misdirected and establishing connections with inappropriate targets. The researchers will also test whether the ability of these receptors to sequester neurotrophins promotes the death of certain neuron populations, using the neurons that innervate the face and nasal passages of rodents as their test system. The results of this research will provide important insights into the causes and consequences of precise control of neurotrophin availability during development, when axons are growing into their target tissues.
