ABSTRACT 9604168 Jonakait Dr. Jonakait's laboratory is interested in finding out what molecules prompt developing neurons to acquire their mature characteristics. They examine developing neurons using cultured cells from embryonic rat brains, and have been particularly interested in a population of cells located in the front part of the base of the brain that use acetylcholine as their chemical transmitter. A neuron that uses acetylcholine as its transmitter is called a "cholinergic" neuron. Having studied this population for some time, they now know that particular kinds of non-neuronal cells in the culture -- cells called microglia -- can be stimulated to produce a molecule that causes immature brain cells in this brain area to become cholinergic. The biochemical nature of this molecule is unknown. Thus, a major goal of this project is to find out, using biochemical techniques, the identity of the molecule. Toward that end, Dr. Jonakait has established a collaboration with Drs. John Winslow and Glenn Hammonds at Genentech, Inc., who are trained biochemists. While the biochemical identity of this possibly novel molecule is being determined, the investigators will ask other biological questions: Will all immature brain cells -- no matter what their normal fate -- be prompted by this molecule to become cholinergic neurons? Alternatively, does the molecule have a more general effect on development, coaxing all immature cells to develop more quickly and efficiently? Importantly, they will also ask whether immature cells, now known to be present even in adult brain, respond to the molecule by assuming cholinergic characteristics.
