Developmental aspect of the gonadotropin-releasing hormone system

Gonadotropin-releasing hormone (GnRH) regulates the hypothalamo-pituitary-gonadal (HPG) axis in all vertebrates studied. GnRH neurons that regulate the HPG axis are primarily derived from progenitor cells in the nasal compartment (NC) and migrate along olfactory system derived fibers across the cribriform plate to destinations in the forebrain. Across their long and uncommon migratory route many factors are likely important for their successful development. Several classes of molecules are being studied for their potential influences on migration, including those related to cell surface interactions (membrane receptors, adhesion molecules, extracellular matrix (ECM) molecules, etc.) and those related to communication across distances (neurotransmitters, peptides, chemoattractant or repellent molecules). Of the classes of molecules associated with cell surface interactions, glycoconjugates with terminal galactose, are temporally and spatially expressed on olfactory fibers that guide GnRH neurons and may play role(s) in migration. Of the molecules associated with communication across distances, the neurotransmitter gamma-aminobutyric acid (GABA) is associated with the GnRH migration pathway and influences the position and organization of GnRH neurons in vitro and in vivo. Furthermore, galactose-containing glycoconjugates and GABA are associated with GnRH neurons in species ranging from humans to lamprey. In mice and rats, GABA is found transiently within a subpopulation of GnRH neurons as they migrate through the NC. One of the key elements in considering regulators of GnRH neuron migration is the diversity of GnRH synthesizing cells. For example, only subpopulations of GnRH neurons also contain GABA, specific GABA receptors, or select glycoconjugates. Similarly, treatments that influence GnRH neuronal migration may only affect specific subsets and not the entire population. It is likely that we will not be able to characterize the migration of all GnRH neurons by a single factor. By combining molecular inquiries with genetic models, single cell analyses, and an in vitro migration model, we are beginning to decipher one of the most critical events in the establishment of the reproductive axis.