Xinyu Duan: Department of Pediatrics, Daping Hospital, Army Medical University, Chongqing, 400010, China.
Xiaoxia Peng: Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, 410078, Hunan, China.
Xiangbin Jia: Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, 410078, Hunan, China.
Senwei Tan: Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, 410078, Hunan, China.
Hui Guo: Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, 410078, Hunan, China.
Jieqiong Tan: Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, 410078, Hunan, China. tanjieqiong@sklmg.edu.cn. ORCID
Zhangxue Hu: Department of Pediatrics, Daping Hospital, Army Medical University, Chongqing, 400010, China. huzx1@163.com.
CELF2 variants have been linked to neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD). However, the molecular mechanisms remain unclear. We generated Celf2 Nestin-Cre knockout mice.Our findings revealed that Celf2 Nestin-Cre heterozygous knockout mice exhibited social impairment and anxiety, an autism-like behavior, though no manifestations of repetitive stereotyped behavior, learning cognitive impairment, or depression were observed. Immunofluorescence assay showed an underdeveloped cerebral cortex with significantly reduced cortical thickness, albeit without abnormal cell density. Further in vitro neuronal culture demonstrated a significant reduction in dendritic spine density and affected synaptic maturation in Celf2 deficient mice, with no notable abnormalities in total neurite and axon length. RNA-seq and RIP-seq analysis of the cerebral cortex revealed differentially expressed genes post Celf2 gene knockout compared with the control group. Enrichment analysis highlighted significant enrichment in dendrite and synapse-related biological processes and pathways. Our study delineated the behavioral and neurodevelopmental phenotypes of Celf2, suggesting its potential involvement in autism through the regulation of target genes associated with dendritic spines and synapse development. Further research is needed to elucidate the specific mechanisms involved.
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Grants
2021YFA0805200/Key Technologies Research and Development Program
2021ZD0201701/National Brain Science and Brain-like Research of China
