Receptor Extracellular Domain Proteins have important functions in the nervous system, including mediating cell adhesion, cell signaling, neurite outgrowth and neuronal arborization patterns. Many human diseases are caused by defects in neuronal patterning that arise during development and/or physiological defects in extracellular receptor functions. The research in this proposal will make use of recently developed collection of plasmids that allow one to rapidly produce and systematically interrogate extracellular receptor domain interactions in a spatiotemporal manner, in an intact developing nervous system. Our previous genomic studies have identified receptor extracellular domain proteins as mediating differences in nervous system development that underlie the potential for complex behaviors. We will examine the role of these proteins in establishing sex-specific differences in nervous system functions that underlie reproductive behaviors.
In humans there are at least 149 genes that encode members of the Extracellular Receptor Immunoglobulin Superfamily. The two founding members that have been the most extensively studied have been linked to several diseases, including mental health disorders, dementias and intellectual disabilities. A mechanistic-level understanding of these genes is essential and is ideally performed in an intact nervous system, so developmental and physiological interactions can be examined in a relevant context. This study will analyze the interactions and functions of this family of proteins in an intact developing nervous system, to understand the mechanisms that when altered cause disease.
