Slitrk gene duplication and expression in the developing zebrafish nervous system

Abstract

The Slitrk family of leucine-rich repeat (LRR) transmembrane proteins bears structural similarity to the Slits and the Trk receptor families, which exert well-established roles in directing nervous system development. Slitrks are less well understood, although they are highly expressed in the developing vertebrate nervous system. Moreover, slitrk variants are associated with several sensory and neuropsychiatric disorders, including myopia, deafness, obsessive-compulsive disorder (OCD), schizophrenia, and Tourette syndrome. Loss-of-function studies in mice show that Slitrks modulate neurite outgrowth and inhibitory synapse formation, although the molecular mechanisms of Slitrk function remain poorly characterized. As a prelude to examining the functional roles of Slitrks, we identified eight slitrk orthologs in zebrafish and observed that seven of the eight orthologs were actively transcribed in the nervous system at embryonic, larval, and adult stages. Similar to previous findings in mice and humans, zebrafish slitrks exhibited unique but overlapping spatial and temporal expression patterns in the developing brain, retina, and spinal cord. Zebrafish express Slitrks in the developing central nervous system at times and locations important to neuronal morphogenesis and synaptogenesis. Future studies will use zebrafish as a convenient, cost-effective model organism to characterize the functional roles of Slitrks in nervous system development.