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ZC4H2 stabilizes RNF220 to pattern ventral spinal cord through modulating Shh/Gli signaling
Pengcheng Ma1,† , Ning-Ning Song2,† , Xiaoning Cheng3,† , Liang Zhu1,4 , Qiong Zhang5 , Long long Zhang1,4 , Xiangcai Yang1,9 , Huishan Wang1,4 , Qinghua Kong6 , Deli Shi3,* , Yu-Qiang Ding2,5,7,* , Bingyu Mao1,8,*
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
2State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Sciences, Fudan University, Shanghai 200032, China
3Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
4Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650223, China
5Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Center for Brain Science, Tongji University School of Medicine, Shanghai 200092, China
6State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650203, China
7Department of Laboratory Animal Science, Fundan University, Shanghai 200032, China
8Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China
9Present address: Department of Clinical Laboratory, The Affiliated Hospital of KMUST, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China
†These authors contributed equally to this work.
*Correspondence to:Deli Shi , Email:dshi@sdu.edu.cn Yu-Qiang Ding , Email:dingyuqiang@vip.163.com; Bingyu Mao , Email:mao@mail.kiz.ac.c
J Mol Cell Biol, Volume 12, Issue 5, May 2020, 337-344,  https://doi.org/10.1093/jmcb/mjz087
Keyword: ZC4H2, RNF220, spinal cord, patterning, Gli signaling

ZC4H2 encodes a C4H2 type zinc-finger nuclear factor, the mutation of which has been associated with disorders with various clinical phenotypes in human, including developmental delay, intellectual disability and dystonia. ZC4H2 has been suggested to regulate spinal cord patterning in zebrafish as a co-factor for RNF220, an ubiquitin E3 ligase involved in Gli signaling. Here we showed that ZC4H2 and RNF220 knockout animals phenocopy each other in spinal patterning in both mouse and zebrafish, with mispatterned progenitor and neuronal domains in the ventral spinal cord. We showed evidence that ZC4H2 is required for the stability of RNF220 and also proper Gli ubiquitination and signaling in vivo. Our data provides new insights into the possible etiology of the neurodevelopmental impairments observed in ZC4H2-associated syndromes.


Volume 12, Issue 5
May 2020