Abstract
The development of Gonadotropin releasing hormone-1 (GnRH) neurons is important for a functional reproduction system in vertebrates. Disruption of GnRH results in hypogonadism and if accompanied by anosmia is termed Kallmann Syndrome (KS). From their origin in the nasal placode, GnRH neurons migrate along the olfactory-derived vomeronasal axons to the nasal forebrain junction and then turn caudally into the developing forebrain. Although research on the origin of GnRH neurons, their migration and genes associated with KS has identified multiple factors that influence development of this system, several aspects still remain unclear. This review discusses development of the olfactory system, factors that regulate GnRH neuron formation and development of the olfactory system, migration of the GnRH neurons from the nose into the brain, and mutations in humans with KS that result from disruption of normal GnRH/olfactory systems development.
Highlights
Unraveling how specialized neurons arise from heterogenous cell populations and migrate to their appropriate location has important implications for understanding the development and progression of neuronal disorders
As the nasal placode invaginates to form the main olfactory epithelium (OE) and the vomeronasal organ (VNO), Gonadotropin releasing hormone-1 (GnRH) neurons migrate out of the VNO to the brain along axons that are covered by olfactory ensheathing cells (OECs) (Figure 1; Wray, 2002a)
The number of GnRH neurons within the forebrain was significantly greater in Cck1R−/− embryos, consistent with an accelerated migratory process. These results indicate that CCK provides an inhibitory influence on GnRH neuronal migration, contributing to the appropriate entrance of these neuroendocrine cells into the brain
Summary
Unraveling how specialized neurons arise from heterogenous cell populations and migrate to their appropriate location has important implications for understanding the development and progression of neuronal disorders. As the nasal placode invaginates to form the main olfactory epithelium (OE) and the vomeronasal organ (VNO), GnRH neurons migrate out of the VNO to the brain along axons that are covered by OECs (Figure 1; Wray, 2002a). PAX6null mice do not develop an eye or nasal placode, and lack olfactory cells and GnRH neurons (Dellovade et al, 1998).
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