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 initiation of mammalian puberty requires an increased secretion of luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling sexual development, from specialized nerve cells (termed neurons) located in a region of the brain known as the hypothalamus. The pubertal increase in LHRH secretion is brought about by changes in the activity of cellular subsets connected to LHRH neurons. Whether such alterations in cell-cell communication are purely biochemical or require plastic rearrangements is not known. This project utilizes a combination of cellular, molecular, and genomic approaches to examine the hypothesis that major changes in expression of three novel families of genes encoding cell-surface molecules implicated in the specification of neural cell communication in the central nervous system are required for the initiation of primate puberty. The project is examining four interrelated hypotheses: 1. That coordinated changes in the hypothalamic expression of neurexins -- a recently discovered, multi-product family of cell-surface proteins thought to play a major role in neuronal cell recognition -- occur at the time of primate puberty. 2. That hypothalamic-specific changes in the expression of particular members of the novel protocadherin-alpha family of adhesion-signaling molecules, recently implicated in the specification of neural cell connectivity, occur at the initiation of puberty. 3. That hypothalamic-specific changes in the expression of a newly discovered family of neurexin-related molecules termed CASPRs (contactin-associated proteins) involved in the communication of neurons with other brain cells termed astrocytes (or astroglial cells), and their interacting molecules, occurs at the time of primate puberty, and 4. That contactin/CASPR-1 and its astroglial recognition molecule (termed receptor protein tyrosine phosphatase-beta) mediate adhesive communication between astroglial cells and LHRH neurons, and that this is an event regulated by growth factors involved in the facilitatory control that glial cells exert on LHRH release during female sexual maturation.