Planar cell polarity and the pathogenesis of Tourette Disorder: New hypotheses and perspectives.
- Authors
- Wu, Junbing; Poppi, Lauren A; Tischfield, Max A
- Year
- 2022
- Journal
- Developmental biology
- PMID
- 35644250
- DOI
- 10.1016/j.ydbio.2022.05.017
Planar cell polarity (PCP) signaling plays a fundamental role in shaping the development and ongoing function of the nervous system, beginning from early stages of neural tube closure and spanning the maintenance of functional synapses in adults. While mutations in core PCP signaling proteins have long been suspected to underlie neural tube closure defects in humans, recent findings also implicate their potential involvement in neurodevelopmental and neuropsychiatric disorders. Missense and loss-of-function mutations in CELSR3, a core component of PCP signaling complexes, are highly associated with Tourette Disorder. Although the functional significance of these mutations has yet to be elucidated in animal and cell models, the expression patterns of Celsr3 in mice point to alterations in cortico-striato-thalamo-cortical circuits. Here, we briefly review the known functions of Celsr3 for nervous system development. We also propose circuit models for Tourette Disorder by hypothesizing roles for Celsr3 in controlling striatal neuromodulation via effects on cholinergic interneurons, and thalamic inhibition through its functions in thalamic reticular nuclei. Testing these and related hypotheses in animal and cell models will move us closer to unraveling the neuropathogenesis of Tourette Disorder, with the ultimate goal of developing more efficacious treatments for both motor and cognitive symptoms.
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder. | 2025 | 40360802 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| A Celsr3 Mutation Linked to Tourette Disorder Disrupts Cortical Dendritic Patterning and Striatal Cholinergic Interneuron Excitability. | Nasello C et al. | — | 2025 | → |
| Genetic advances and translational phenotypes in rodent models for Tourette disorder. | Kowalski TF et al. | — | 2025 | → |
| Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder. | Strom NI et al. | — | 2025 | → |
| Human mutations in high-confidence Tourette disorder genes affect sensorimotor behavior, reward learning, and striatal dopamine in mice. | Nasello C et al. | — | 2024 | → |
| Emerging roles of planar cell polarity proteins in glutamatergic synapse formation, maintenance and function in health and disease. | Freitas AE et al. | — | 2023 | → |
| Human mutations in high-confidence Tourette disorder genes affect sensorimotor behavior, reward learning, and striatal dopamine in mice | Nasello C et al. | — | 2023 | — |