机构：[1]Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, Key Lab of Rare Pediatric Diseases of Ministry of Education, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.[2]State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.[3]Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, Hunan 410078, China.[4]Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou 350005, China.[5]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.神经科系统神经内科首都医科大学宣武医院
KCTD10 belongs to the KCTD (potassiumchannel tetramerization domain) family, many members of which are associated with neuropsychiatric disorders. However, the biological function underlying the association with brain disorders remains to be explored. Here, we reveal that Kctd10 is highly expressed in neuronal progenitors and layer V neurons throughout brain development. Kctd10 deficiency triggers abnormal proliferation and differentiation of neuronal progenitors, reduced deep-layer (especially layer V) neurons, increased upper-layer neurons, and lowered brain size. Mechanistically, we screened and identified a unique KCTD10-interacting protein, KCTD13, associated with neurodevelopmental disorders. KCTD10 mediated the ubiquitination-dependent degradation of KCTD13 and KCTD10 ablation resulted in a considerable increase of KCTD13 expression in the developing cortex. KCTD13 overexpression in neuronal progenitors led to reduced proliferation and abnormal cell distribution, mirroring KCTD10 deficiency. Notably, mice with brain-specific Kctd10 knockout exhibited obvious motor deficits. This study uncovers the physiological function of KCTD10 and provides unique insights into the pathogenesis of neurodevelopmental disorders.
基金：
This work was partially supported by National Natural Science Foundation of China (32070980, 32271026,81901168, 32330038 and 32394030), Huxiang Young Talents Program(2020RC3006, 2022RC1163), Natural Science Foundation of Hunan Province(2021JJ20075, 2020JJ4689, 2018DK201, 2022JJ20056 and 2019JJ40408),Innovation Driven Project of Central South University (2020CX022), Open Projectof Chinese Academy of Sciences (2022-MDB-KF-24); This work was also supportedby the High Performance Computing Center of Central South University.
第一作者机构：[1]Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, Key Lab of Rare Pediatric Diseases of Ministry of Education, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
共同第一作者：
通讯作者：
通讯机构：[1]Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, Key Lab of Rare Pediatric Diseases of Ministry of Education, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.[3]Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, Hunan 410078, China.
推荐引用方式(GB/T 7714)：
Cheng Jianbo,Wang Zhen,Tang Manpei,et al.KCTD10 regulates brain development by destabilizing brain disorder-associated protein KCTD13[J].Proceedings Of The National Academy Of Sciences Of The United States Of America.2024,121(12):e2315707121.doi:10.1073/pnas.2315707121.
APA：
Cheng Jianbo,Wang Zhen,Tang Manpei,Zhang Wen,Li Guozhong...&Yuan Ling.(2024).KCTD10 regulates brain development by destabilizing brain disorder-associated protein KCTD13.Proceedings Of The National Academy Of Sciences Of The United States Of America,121,(12)
MLA：
Cheng Jianbo,et al."KCTD10 regulates brain development by destabilizing brain disorder-associated protein KCTD13".Proceedings Of The National Academy Of Sciences Of The United States Of America 121..12(2024):e2315707121
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