This is a Shannon Award providing partial support for research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. The long-term objective of this research is to characterize and investigate the role of the nervus terminalis (terminal nerve), in mammals, as an intermediary in the relay of chemical signals from the external environment to the neuroendocrine cells of the brain and to determine if it acts alone or in concert with the olfactory, vomeronasal and/or trigeminal nerves. The recent discovery that luteinizing hormone- releasing hormone (LHRH) neurons (along with ganglion cells of the terminal nerve) originate in the epithelium of the medial olfactory pit and migrate into the brain along axons of the terminal nerve, opens new areas of investigation including a possible connection between the olfactory, accessory olfactory and the LHRH neuroendocrine systems. The specific objectives of this investigation are: I. Test the hypothesis that all LHRH neurons originate in the medial olfactory placode and migrate into the forebrain along branches of the terminal nerve. Surgical removal of the olfactory placode or target tissue forebrain in whole mouse embryos in culture or explants of brain and nasal regions will be used to test the placodal origin of LHRH neurons. II. Test the hypothesis that LHRH cell migration takes place along axons of the terminal nerve and is dependent on chemical or molecular signals within the migration route. II A. 1) The chemical makeup of the migration route will be examined with antibodies and/or probes to cell adhesion molecules (including L1, Cadherins, Integrins, Contactin). Glial (S100) or neuronal (NSE) markers will be used to examine the distribution of neurons and/or glia along the migration route of LHRH cells from the nose into the forebrain. II A. 2) Investigate the function of components found on the migration route by introduction of antibodies or antagonists to these components to disrupt migration. II B. 1) Investigate the role of retinoid signalling in induction and differentiation of the medial olfactory placode and derivatives, including the terminal nerve and the origin and migration of LHRH neurons using in situ hybridization with probes or antibodies for the retinoic acid receptors RAR-, RAR-beta, and RAR-combined with immunocytochemical localization of LHRH. II B. 2) Investigate the function of these receptors by injections of antibodies or anti-sense oligonucleotides to specific retinoic acid receptors in vivo or in cultured whole mouse embryos or explants of brain and nasal tissue. III. Examine the development of the terminal nerve in humans and test the hypothesis that the origin and migration of LHRH neurons is conserved throughout vertebrate evolution. Study of the development of the terminal nerve and the migration of LHRH neurons in human embryos 46 days and older will provide a definitive description of this phenomenon in humans. The focus of this study is on the course of LHRH neurons through the forebrain.
