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. This project is examining the hypothesis that growth factor molecules known as neurotrophins, and chemical messengers required for the development and mature function of the nervous system are produced by the mammalian ovary and contribute to regulating critical developmental phases in the natural history of the gland. The analysis of mutant mice carrying deletions of the genes encoding either neurotrophins or their recognition molecules (i.e., the neurotrophin receptors) showed that these growth factors are required for early development of ovarian follicles (the structural and functional unit of the ovary). In addition to neurotrophins, the ovary produces a variety of the same chemical messengers required for neuron-to-neuron communication in the nervous system. These messengers, known as neurotransmitters, appear to contribute to the process by which follicles become differentiated during early development and acquire the capability of responding to those hormones that -- secreted by the pituitary gland -- control the growth of mature follicles before puberty and during adult reproductive life. Our studies also demonstrated that the ovaries of nonhuman primates contain neurons, i.e., the same cells required for the function of the nervous system. These ovarian neurons produce neurotransmitters and are able to recognize neurotrophins. They originate during early gestation from the same region of the embryo that gives rise to neurons of the peripheral nervous system. Together, these findings demonstrate the unexpected involvement of molecules previously thought to operate within the nervous system in the control of ovarian development.