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Kallmann syndrome is a human genetic disorder characterized by a defect in olfactory system development due to an abnormality in the migration of olfactory axons and of gonadotropin releasing hormone (Gn-RH) producing neurons. The predicted protein product of the recently isolated gene for X-linked Kallmann syndrome shares motifs with molecules involved in neural development. We have isolated the chicken Kallmann syndrome gene which shows an overall 77% amino acid identity with the human homologue. The degree of identity increases within the putative functional domains, strongly supporting their functional relevance. Expression studies have been performed by Northern analysis, RT-PCR, RNase protection and in situ hybridization in chicken embryos at different developmental stages. In the developing and adult chicken, high levels of expression of this gene were found in the olfactory bulb and in the cerebellar cortex, both areas affected in patients with Kallmann syndrome. In the olfactory bulb, the gene is expressed by the mitral cells, the target of olfactory axons; in the cerebellum, expression was found in the Purkinje cells. The site and the timing of expression of the Kallmann syndrome gene within the olfactory system suggest that its protein product is a signal molecule required for proper neuronal targeting throughout life.