SDF and GABA interact to regulate axophilic migration of GnRH neurons

Abstract

Stromal derived growth factor (SDF-1) and Gamma-aminobutyric acid (GABA) are two extracellular cues that regulate the rate of neuronal migration during development and may, in fact, act synergistically. The molecular mechanisms of this interaction are still unclear. Gonadotropin releasing hormone-1 (GnRH) neurons are essential for vertebrate reproduction. During development, these neurons emerge from the nasal placode and migrate through the cribriform plate into the brain. Both SDF-1 and GABA have been shown to regulate the rate of GnRH neuronal migration by accelerating and slowing migration, respectively. As, such, this system was used to explore the mechanism by which these molecules act to produce coordinated cell movement during development. In the present study, GABA and SDF-1 are shown to exert opposite effects on the speed of cell movement by activating depolarizing or hyperpolarizing signaling pathways, GABA via changes in chloride and SDF-1 via changes in potassium. GABA and SDF-1 were also found to act synergistically to promote linear rather than random movement. The simultaneous activation of these signaling pathways therefore results in tight control of cellular speed and improved directionality along the migratory pathway of GnRH neurons.