title: Developmentally regulated and evolutionarily conserved expression of SLITRK1 in brain circuits implicated in Tourette syndrome.
abstract: Tourette syndrome (TS) is an inherited developmental neuropsychiatric disorder characterized by vocal and motor tics. Multiple lines of neurophysiological evidence implicate dysfunction in the corticostriatal-thalamocortical circuits in the etiology of TS. We recently identified rare sequence variants in the Slit and Trk-like family member 1 (SLITRK1) gene associated with TS. SLITRK1, a single-pass transmembrane protein, displays similarities to the SLIT family of secreted ligands, which have roles in axonal repulsion and dendritic patterning, but its function and developmental expression remain largely unknown. Here we provide evidence that SLITRK1 has a developmentally regulated expression pattern in projection neurons of the corticostriatal-thalamocortical circuits. SLITRK1 is further enriched in the somatodendritic compartment and cytoplasmic vesicles of cortical pyramidal neurons in mouse, monkey, and human brain, observations suggestive of an evolutionarily conserved function in mammals. SLITRK1 is transiently expressed in the striosomal/patch compartment of the mammalian striatum and moreover is associated with the direct output pathway; adult striatal expression is confined to cholinergic interneurons. These analyses demonstrate that the expression of SLITRK1 is dynamic and specifically associated with the circuits most commonly implicated in TS and related disorders, suggesting that SLITRK1 contributes to the development of corticostriatal-thalamocortical circuits.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Althea A
authors.initials: AA
authors.lastname: Stillman
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Krsnik
authors.forename: Jinhao
authors.initials: J
authors.lastname: Sun
authors.forename: Mladen-Roko
authors.initials: MR
authors.lastname: Rasin
authors.forename: Matthew W
authors.initials: MW
authors.lastname: State
authors.forename: Nenad
authors.initials: N
authors.lastname: Sestan
authors.forename: Angeliki
authors.initials: A
authors.lastname: Louvi
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000033:anatomy & histology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D005879:Tourette Syndrome / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C480569:Slitrk protein, mouse