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

• 作者: Lin Ma Yanhua Du Xiangjie Xu Hexi Feng Yi Hui Nan Li Guanyu Jiang Xiaoqing Zhang Xiaocui Li Ling Liu
• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2022,（1）
• 所属期刊栏目: Original Articles
• 页码范围: 81-94
• 页数: 14页
• 语种: 英文

摘要

Congenital hydrocephalus is a major neurolog-ical disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mecha-nisms remain largely unknown.Reproducible animal models mirroring both embryonic and postnatal hydro-cephalus 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 hydro-cephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.