The neuropeptide somatostatin (SS) is widely distributed in the central nervous system and peripheral tissues. In the developing brain, there is evidence that SS plays an important role in neuronal development. Transient expression of SS has been found in the olfactory-forebrain region of chick embryos. The times of appearance and distribution of SS immunoreactive (-ir) neural elements are similar to those of GnRH neurons which originate in the olfactory placode and migrate into the forebrain. Based on these results, it has been postulated that SS may play a role in development of GnRH neurons and olfactory axons. Recent study has shown that suppression of SS mRNA in the olfactory epithelium by small interfering RNA (siRNA) at embryonic day (E) 3.5 induced remarkable reduction in the number of migrating GnRH neurons at E5.5. The number of apoptotic cells in the olfactory epithelium was not affected by siRNA for SS mRNA. From these results, it is likely that SS affects the migratory process of GnRH neurons. To further examine the effect of SS on the migration of GnRH neurons, olfactory placode explant culture was used. Olfactory placode explants from E3.5 chick embryos were treated with SS (1nM), octreotide, an SS analog (100nM), and Neurobasal medium as a control once at 2-3 hours later, twice per day on 1-3 days in vitro (div). Explants were fixed on 4 div and processed for triple immunofluorescence labeling for GnRH, the highly polysialylated form of NCAM (PSA) and SS. The total number of GnRH neurons migrated off the explants was significantly increased by the octreotide treatment. The migration distance of GnRH neurons into the gel from the peripheral site of the explant was significantly more increased in explants treated with SS and octreotide than in those without stimulants. Moreover, the diameter of PSA-ir fibers was measured at 100 μm away from the peripheral site of the explants and found that the rate of PSA-ir fibers above 2 μm in diameter was significantly more increased in the treated groups than the control ones. These results indicate that SS exerts facilitatory influences on GnRH neuron migration and olfactory axon development.