Neural expression of the transcription factor THAP1 during development in rat.


Neural expression of the transcription factor THAP1 during development in rat.

Neuroscience. 2012 Dec 5. pii: S0306-4522(12)01160-8. doi: 10.1016/j.neuroscience.2012.11.049.

Loss of function mutations in THAP1 have been associated with primary generalized and focal dystonia in children and adults. THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger domain and plays a critical role in G(1)-S cell cycle control. Current thinking suggests that dystonia may be a neurodevelopmental circuit disorder. Hence, THAP1 may participate in the development of the nervous system. Herein, we report the neurodevelopmental expression patterns of Thap1 transcript and THAP1 protein from the early postnatal period through adulthood in rat brain, spinal cord and dorsal root ganglia (DRG). We detected Thap1 transcript and THAP1-immunoreactivity (IR) in cerebral cortex, cerebellum, striatum, substantia nigra, thalamus, spinal cord and DRG. Thap1 transcript expression was higher in brain than in spinal cord and DRG at P1 and P7 and declined to similar levels at P14 and later time points in all regions except cerebellum, where it remained high through adulthood. In brain, THAP1 expression was highest in early development, particularly in cerebellum at P7. In addition to Purkinje cells in the cerebellum, THAP1-IR was also localized to pyramidal neurons in cerebral cortex, relay neurons in thalamus, medium spiny and cholinergic neurons in striatum, dopaminergic neurons in substantia nigra, and pyramidal and interneurons in hippocampus. In cerebellar cortex, THAP1-IR was prominently distributed in the perikarya and proximal dendrites of Purkinje cells at early time-points. In contrast, it was more diffusely distributed throughout the dendritic arbor of adult Purkinje cells producing a moderate diffuse staining pattern in the molecular layer. At all time points, nuclear IR was weaker than cytoplasmic IR. The prominent cytoplasmic and developmentally-regulated expression of THAP1 suggests that THAP1 may function as part of a cell surface-nucleus signaling cascade involved in terminal neural differentiation.

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