β-Catenin Deletion in Regional Neural Progenitors Leads to Congenital Hydrocephalus in Mice.
10.1007/s12264-021-00763-z
- Author:
Lin MA
1
;
Yanhua DU
2
;
Xiangjie XU
1
;
Hexi FENG
1
;
Yi HUI
1
;
Nan LI
1
;
Guanyu JIANG
3
;
Xiaoqing ZHANG
4
;
Xiaocui LI
5
;
Ling LIU
6
Author Information
1. Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
2. Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
3. Key Laboratory of Neuroregeneration of Shanghai Universities, School of Medicine, Tongji University, Shanghai, 200092, China.
4. Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China. xqzhang@tongji.edu.cn.
5. Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. sisi1113@163.com.
6. Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China. lliu@tongji.edu.cn.
- Publication Type:Journal Article
- Keywords:
Congenital hydrocephalus;
Ependymal cells;
Neural development;
Nkx2.1;
β-Catenin
- MeSH:
Animals;
Disease Models, Animal;
Hydrocephalus/genetics*;
Mice;
Mice, Knockout;
Neurons;
beta Catenin/genetics*
- From:
Neuroscience Bulletin
2022;38(1):81-94
- CountryChina
- Language:English
-
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.
