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 providesnew insights into the possible etiology of the neurodevelopmental impairments observed in ZC4H2-associated syndromes.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31871483, 31671521, 31500847, 31771134, 81571332, 91232724, 31671509]; National Key R&D Program of China [2017YFA0104002]; Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]; ZJLab
第一作者机构:[1]Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China[2]Fudan Univ, Inst Brain Sci, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China[3]Fudan Univ, Inst Brain Sci, MOE Frontiers Ctr Brain Sci, Shanghai 200032, Peoples R China[6]Tongji Univ, Sch Med, East Hosp, Key Lab Arrhythmias,Minist Educ China, Shanghai 200092, Peoples R China[7]Tongji Univ, Sch Med, Dept Anat & Neurobiol, Collaborat Innovat Ctr Brain Sci, Shanghai 200092, Peoples R China[9]Fundan Univ, Dept Lab Anim Sci, Shanghai 200032, Peoples R China[10]Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China
推荐引用方式(GB/T 7714):
Ma Pengcheng,Song Ning-Ning,Cheng Xiaoning,et al.ZC4H2 stabilizes RNF220 to pattern ventral spinal cord through modulating Shh/Gli signaling[J].JOURNAL OF MOLECULAR CELL BIOLOGY.2020,12(5):337-344.doi:10.1093/jmcb/mjz087.
APA:
Ma, Pengcheng,Song, Ning-Ning,Cheng, Xiaoning,Zhu, Liang,Zhang, Qiong...&Mao, Bingyu.(2020).ZC4H2 stabilizes RNF220 to pattern ventral spinal cord through modulating Shh/Gli signaling.JOURNAL OF MOLECULAR CELL BIOLOGY,12,(5)
MLA:
Ma, Pengcheng,et al."ZC4H2 stabilizes RNF220 to pattern ventral spinal cord through modulating Shh/Gli signaling".JOURNAL OF MOLECULAR CELL BIOLOGY 12..5(2020):337-344