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β-Catenin Deletion in Regional Neural Progenitors Leads to Congenital Hydrocephalus in Mice

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Abstract

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality; however, the underlying cellular and molecular mechanisms remain largely unknown. Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited. Here, we describe a new mouse model of congenital hydrocephalus through knockout of β-catenin in Nkx2.1-expressing regional neural progenitors. Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood. Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis after β-catenin knockout. Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages. Thus, knockout of β-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.

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Acknowledgements

This work was supported by grants from the National Key Research and Development Program of China (2018YFA0108000 and 2019YFA0110300), the National Natural Science Foundation of China (8205020, 32000689, 31400934, 31771132, 31872760, 31801204, and 31800858), the Science and Technology Commission of Shanghai Municipality (19JC1415100 and 21140902300), the Shanghai Municipal Education Commission (C120114), China Postdoctoral Science Foundation (2017M621526), the Fundamental Research Funds for the Central Universities, and the Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone (Stem Cell Strategic Biobank and Clinical Translation Platform of Stem Cell Technology, ZJ2018-ZD-004).

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Authors and Affiliations

  1. Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China

    Lin Ma, Xiangjie Xu, Hexi Feng, Yi Hui, Nan Li, Xiaoqing Zhang & Ling Liu

  2. Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Orthopaedic Department of Tongji Hospital, Shanghai, 200065, China

    Xiaoqing Zhang

  3. Brain and Spinal Cord Innovative Research Center, School of Medicine, Tongji University, Shanghai, 200092, China

    Xiaoqing Zhang

  4. Key Laboratory of Neuroregeneration of Shanghai Universities, School of Medicine, Tongji University, Shanghai, 200092, China

    Lin Ma, Xiangjie Xu, Hexi Feng, Yi Hui, Nan Li, Guanyu Jiang & Ling Liu

  5. Tsingtao Advanced Research Institute, Tongji University, Qingdao, 266071, China

    Xiaoqing Zhang

  6. Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200120, China

    Lin Ma, Xiangjie Xu, Hexi Feng, Yi Hui, Nan Li, Xiaoqing Zhang & Ling Liu

  7. Department of Pathology and Pathophysiology, School of Medicine, Tongji University, Shanghai, 200092, China

    Lin Ma & Ling Liu

  8. Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Yanhua Du

  9. Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China

    Xiaocui Li

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  1. Lin Ma
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  2. Yanhua Du
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  3. Xiangjie Xu
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  4. Hexi Feng
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  9. Xiaocui Li
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Correspondence to Xiaoqing Zhang, Xiaocui Li or Ling Liu.

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Ma, L., Du, Y., Xu, X. et al. β-Catenin Deletion in Regional Neural Progenitors Leads to Congenital Hydrocephalus in Mice. Neurosci. Bull. 38, 81–94 (2022). https://doi.org/10.1007/s12264-021-00763-z

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