kal-1, the functional homologue of human Kallmann syndrome gene KAL1, is required for the neurite branching in subsets of embryonic motoneurons in Drosophila melanogaster

Abstract

Kallmann syndrome is an inherited disorder of hypogonadotropic hypogonadism and anosmia owing to lesions in axonal organization and disrupted cell migration of neuroblasts from developing olfactory epithelium. The gene responsible for the X-linked type of Kallmann syndrome, KAL1, encodes an extracellular matrix protein, Anosmin1 that is related to members of neuronal cell adhesion protein family. The interspecies studies for Anosmin function in C. elegance showed that the nematode homologue of kal-1 is required for axonal outgrowth and epidermal migration in developing embryos. For the detailed biological analysis for the KAL1 Anosmin, we isolated the Drosophila KAL1 homologue, kal-1, and generated its mutants by P-element mobilization. The kal-1 embryos showed impaired axonal branching: SNb motor neurons could not extend their axons to proper muscle targets, and the exterior longitudinal FasII-expressing axon bundles were openly misconnected. Specific a α -Kal-1 serum was generated, and revealed dynamic expressions during various morphogenetic processes such as the germ band retraction as well as head sensory organs and segmentally repeated expressions in several subsets of motor neurons. These results suggest that the Drosophila Kal-1 has roles in neurite branching and cell adhesion during the embryogenesis as a functional homologue of nematode and vertebrate KAL1s.