Neural expression of the transcription factor THAP1 during development in rat

Y. Zhao, Jianfeng Xiao, S. Gong, J. A. Clara, Mark Ledoux

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Loss of function mutations in THAP1 has 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 G1-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 the rat brain, spinal cord and dorsal root ganglia (DRG). We detected Thap1 transcript and THAP1-immunoreactivity (IR) in the cerebral cortex, cerebellum, striatum, substantia nigra, thalamus, spinal cord and DRG. Thap1 transcript expression was higher in the 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 the cerebellum, where it remained high through adulthood. In the brain, THAP1 expression was highest in early development, particularly in the cerebellum at P7. In addition to Purkinje cells in the cerebellum, THAP1-IR was also localized to pyramidal neurons in the cerebral cortex, relay neurons in the thalamus, medium spiny and cholinergic neurons in the striatum, dopaminergic neurons in the substantia nigra, and pyramidal and interneurons in the hippocampus. In the 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.

Original languageEnglish (US)
Pages (from-to)282-295
Number of pages14
JournalNeuroscience
Volume231
DOIs
StatePublished - Feb 2 2013

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Cerebellum
Spinal Nerve Roots
Purkinje Cells
Spinal Ganglia
Transcription Factors
Dystonic Disorders
Spinal Cord
Substantia Nigra
Thalamus
Cerebral Cortex
Brain
Cerebellar Cortex
Cholinergic Neurons
Dystonia
Pyramidal Cells
Dopaminergic Neurons
Zinc Fingers
Interneurons
Dendrites
Cell Cycle Checkpoints

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Neural expression of the transcription factor THAP1 during development in rat. / Zhao, Y.; Xiao, Jianfeng; Gong, S.; Clara, J. A.; Ledoux, Mark.

In: Neuroscience, Vol. 231, 02.02.2013, p. 282-295.

Research output: Contribution to journalArticle

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abstract = "Loss of function mutations in THAP1 has 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 G1-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 the rat brain, spinal cord and dorsal root ganglia (DRG). We detected Thap1 transcript and THAP1-immunoreactivity (IR) in the cerebral cortex, cerebellum, striatum, substantia nigra, thalamus, spinal cord and DRG. Thap1 transcript expression was higher in the 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 the cerebellum, where it remained high through adulthood. In the brain, THAP1 expression was highest in early development, particularly in the cerebellum at P7. In addition to Purkinje cells in the cerebellum, THAP1-IR was also localized to pyramidal neurons in the cerebral cortex, relay neurons in the thalamus, medium spiny and cholinergic neurons in the striatum, dopaminergic neurons in the substantia nigra, and pyramidal and interneurons in the hippocampus. In the 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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