Developmentally regulated and evolutionarily conserved expression of SLITRK1 in brain circuits implicated in Tourette syndrome
Open accessAbstract
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. J. Comp. Neurol. 513:21–37, 2009. © 2008 Wiley‐Liss, Inc.
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SLITRK1 expression in mouse, monkey, and human brain is developmentally regulated in the neuroanatomical circuits most commonly implicated in TS.
“SLITRK 1 expression in mouse, monkey, and human brain is developmentally regulated in the neuroanatomical circuits most commonly implicated in TS [616].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [616]
In the striatum, SLITRK1 expression is high in striosomes/patches during early brain development but significantly diminishes later, suggesting a possible role in establishing corticostriatal circuitry.
“In the striatum, SLITRK 1 expression is high in striosomes/patches during early brain development but significantly diminishes later, suggesting a possible role in establishing corticostriatal circuitry.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [616]
SLITRK1 expression is restricted to striatal projection neurons of the direct pathway where it could influence striatal circuitry.
“In addition, SLITRK 1 expression is also restricted to striatal projection neurons of the direct pathway where it could influence striatal circuitry”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [616]
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- Authors
- Stillman, A. A., Krsnik, Ž., Sun, J., Rašin, M., State, M. W., šestan, N., & Louvi, A.
- Affiliations
- Yale University (US)
- Corresponding author
- Louvi, Angeliki
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2008-12-22
- Volume
- 513
- Issue
- 1
- Pages
- 21-37
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- PMC
- PMC3292218
- OpenAlex
- W2010319576
- Cited by
- 95
- References
- 92
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 9 · 2013: 8 · 2012: 13
- FWCI
- 9.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Autism Speaks
- Yale University
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS054273, R01NS056276)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- SLITRK1, Tourette syndrome, developmental gene expression, striatum, cholinergic interneurons, cortical pyramidal neurons, evolutionarily conserved function, tics, neuropsychiatric disorders
- MeSH terms
- Animals, Brain, Tourette Syndrome, Humans, Immunohistochemistry, Macaca mulatta, Membrane Proteins, Nerve Tissue Proteins, Neural Pathways, Neurons, Gene Expression Regulation, Developmental, Mice
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