The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development
Summary: Eliminating redundant synapses formed around birth is essential for shaping functionally mature neural circuits during postnatal development. Each Purkinje cell (PC) in the neonatal mouse cerebellum receives synaptic inputs from multiple climbing fibers (CFs). Only one CF is strengthened an...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225010077 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849722126343340032 |
|---|---|
| author | Jianling Zhang Takaki Watanabe Taisuke Miyazaki Miwako Yamasaki Kohtarou Konno Yuto Okuno Kyoko Matsuyama Takayuki Noro Masahiko Watanabe Naofumi Uesaka Masanobu Kano |
| author_facet | Jianling Zhang Takaki Watanabe Taisuke Miyazaki Miwako Yamasaki Kohtarou Konno Yuto Okuno Kyoko Matsuyama Takayuki Noro Masahiko Watanabe Naofumi Uesaka Masanobu Kano |
| author_sort | Jianling Zhang |
| collection | DOAJ |
| description | Summary: Eliminating redundant synapses formed around birth is essential for shaping functionally mature neural circuits during postnatal development. Each Purkinje cell (PC) in the neonatal mouse cerebellum receives synaptic inputs from multiple climbing fibers (CFs). Only one CF is strengthened and extends its innervation over PC dendrites, whereas the other CFs are eventually pruned during postnatal development. These events are believed to require proper gene expression, but the underlying mechanisms are not yet understood. Here, we report that the transcription factor ZFP64 in PCs mediates part of CF synapse elimination events presumably downstream of P/Q-type voltage-dependent Ca2+ channels (P/Q-VDCCs). PC-specific knockdown (KD) of ZFP64 during postnatal development delayed the elimination of redundant CF synapses and the dendritic extension of CF innervation. The KD of semaphorin 3A (Sema3A) in PCs partially restored the effects of ZFP64 or P/Q-VDCC KD. We propose that ZFP64 promotes developmental CF synapse elimination by regulating Sema3A expression. |
| format | Article |
| id | doaj-art-6a19dcc7edf3403f925628fffcaeec71 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-6a19dcc7edf3403f925628fffcaeec712025-08-20T03:11:26ZengElsevieriScience2589-00422025-06-0128611274610.1016/j.isci.2025.112746The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar developmentJianling Zhang0Takaki Watanabe1Taisuke Miyazaki2Miwako Yamasaki3Kohtarou Konno4Yuto Okuno5Kyoko Matsuyama6Takayuki Noro7Masahiko Watanabe8Naofumi Uesaka9Masanobu Kano10Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo 113-0033, JapanDepartment of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo 113-0033, Japan; Advanced Comprehensive Research Organization (ACRO), Teikyo University, Tokyo 173-0003, Japan; Corresponding authorDepartment of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, JapanDepartment of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, JapanDepartment of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, JapanDepartment of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Advanced Comprehensive Research Organization (ACRO), Teikyo University, Tokyo 173-0003, JapanDepartment of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, JapanDepartment of Cognitive Neurobiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, JapanDepartment of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo 113-0033, Japan; Advanced Comprehensive Research Organization (ACRO), Teikyo University, Tokyo 173-0003, Japan; Corresponding authorSummary: Eliminating redundant synapses formed around birth is essential for shaping functionally mature neural circuits during postnatal development. Each Purkinje cell (PC) in the neonatal mouse cerebellum receives synaptic inputs from multiple climbing fibers (CFs). Only one CF is strengthened and extends its innervation over PC dendrites, whereas the other CFs are eventually pruned during postnatal development. These events are believed to require proper gene expression, but the underlying mechanisms are not yet understood. Here, we report that the transcription factor ZFP64 in PCs mediates part of CF synapse elimination events presumably downstream of P/Q-type voltage-dependent Ca2+ channels (P/Q-VDCCs). PC-specific knockdown (KD) of ZFP64 during postnatal development delayed the elimination of redundant CF synapses and the dendritic extension of CF innervation. The KD of semaphorin 3A (Sema3A) in PCs partially restored the effects of ZFP64 or P/Q-VDCC KD. We propose that ZFP64 promotes developmental CF synapse elimination by regulating Sema3A expression.http://www.sciencedirect.com/science/article/pii/S2589004225010077Molecular physiologyNeuroscienceDevelopmental biology |
| spellingShingle | Jianling Zhang Takaki Watanabe Taisuke Miyazaki Miwako Yamasaki Kohtarou Konno Yuto Okuno Kyoko Matsuyama Takayuki Noro Masahiko Watanabe Naofumi Uesaka Masanobu Kano The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development iScience Molecular physiology Neuroscience Developmental biology |
| title | The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development |
| title_full | The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development |
| title_fullStr | The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development |
| title_full_unstemmed | The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development |
| title_short | The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development |
| title_sort | transcription factor zfp64 promotes activity dependent synapse elimination during postnatal cerebellar development |
| topic | Molecular physiology Neuroscience Developmental biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225010077 |
| work_keys_str_mv | AT jianlingzhang thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT takakiwatanabe thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT taisukemiyazaki thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT miwakoyamasaki thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT kohtaroukonno thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT yutookuno thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT kyokomatsuyama thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT takayukinoro thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT masahikowatanabe thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT naofumiuesaka thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT masanobukano thetranscriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT jianlingzhang transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT takakiwatanabe transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT taisukemiyazaki transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT miwakoyamasaki transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT kohtaroukonno transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT yutookuno transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT kyokomatsuyama transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT takayukinoro transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT masahikowatanabe transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT naofumiuesaka transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment AT masanobukano transcriptionfactorzfp64promotesactivitydependentsynapseeliminationduringpostnatalcerebellardevelopment |