Heterozygous FOXJ1 Mutations Cause Incomplete Ependymal Cell Differentiation and Communicating Hydrocephalus.

IF 3.6 4区 医学 Q3 CELL BIOLOGY Cellular and Molecular Neurobiology Pub Date : 2023-11-01 Epub Date: 2023-08-24 DOI:10.1007/s10571-023-01398-6
Connie C Hou, Danielle Li, Bethany C Berry, Shaokuan Zheng, Rona S Carroll, Mark D Johnson, Hong Wei Yang
{"title":"Heterozygous FOXJ1 Mutations Cause Incomplete Ependymal Cell Differentiation and Communicating Hydrocephalus.","authors":"Connie C Hou, Danielle Li, Bethany C Berry, Shaokuan Zheng, Rona S Carroll, Mark D Johnson, Hong Wei Yang","doi":"10.1007/s10571-023-01398-6","DOIUrl":null,"url":null,"abstract":"<p><p>Heterozygous mutations affecting FOXJ1, a transcription factor governing multiciliated cell development, have been associated with obstructive hydrocephalus in humans. However, factors that disrupt multiciliated ependymal cell function often cause communicating hydrocephalus, raising questions about whether FOXJ1 mutations cause hydrocephalus primarily by blocking cerebrospinal fluid (CSF) flow or by different mechanisms. Here, we show that heterozygous FOXJ1 mutations are also associated with communicating hydrocephalus in humans and cause communicating hydrocephalus in mice. Disruption of one Foxj1 allele in mice leads to incomplete ependymal cell differentiation and communicating hydrocephalus. Mature ependymal cell number and motile cilia number are decreased, and 12% of motile cilia display abnormal axonemes. We observed decreased microtubule attachment to basal bodies, random localization and orientation of basal body patches, loss of planar cell polarity, and a disruption of unidirectional CSF flow. Thus, heterozygous FOXJ1 mutations impair ventricular multiciliated cell differentiation, thereby causing communicating hydrocephalus. CSF flow obstruction may develop secondarily in some patients harboring FOXJ1 mutations. Heterozygous FOXJ1 mutations impair motile cilia structure and basal body alignment, thereby disrupting CSF flow dynamics and causing communicating hydrocephalus.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661798/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular and Molecular Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10571-023-01398-6","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/24 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Heterozygous mutations affecting FOXJ1, a transcription factor governing multiciliated cell development, have been associated with obstructive hydrocephalus in humans. However, factors that disrupt multiciliated ependymal cell function often cause communicating hydrocephalus, raising questions about whether FOXJ1 mutations cause hydrocephalus primarily by blocking cerebrospinal fluid (CSF) flow or by different mechanisms. Here, we show that heterozygous FOXJ1 mutations are also associated with communicating hydrocephalus in humans and cause communicating hydrocephalus in mice. Disruption of one Foxj1 allele in mice leads to incomplete ependymal cell differentiation and communicating hydrocephalus. Mature ependymal cell number and motile cilia number are decreased, and 12% of motile cilia display abnormal axonemes. We observed decreased microtubule attachment to basal bodies, random localization and orientation of basal body patches, loss of planar cell polarity, and a disruption of unidirectional CSF flow. Thus, heterozygous FOXJ1 mutations impair ventricular multiciliated cell differentiation, thereby causing communicating hydrocephalus. CSF flow obstruction may develop secondarily in some patients harboring FOXJ1 mutations. Heterozygous FOXJ1 mutations impair motile cilia structure and basal body alignment, thereby disrupting CSF flow dynamics and causing communicating hydrocephalus.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
杂合子FOXJ1突变导致室管膜细胞分化不完全和通讯性脑积水。
影响FOXJ1(一种控制多纤毛细胞发育的转录因子)的杂合突变与人类阻塞性脑积水有关。然而,破坏多根室管膜细胞功能的因素经常导致通讯性脑积水,这就提出了FOXJ1突变是否主要通过阻断脑脊液(CSF)流动或通过其他机制导致脑积水的问题。在这里,我们发现杂合子FOXJ1突变也与人类的通讯性脑积水有关,并引起小鼠的通讯性脑积水。小鼠Foxj1等位基因的破坏可导致室管膜细胞分化不完全和通讯性脑积水。室管膜成熟细胞数量和运动纤毛数量减少,12%的运动纤毛轴突异常。我们观察到微管与基底体的附着减少,基底体斑块的随机定位和定向,平面细胞极性的丧失,以及单向CSF流动的中断。因此,杂合的FOXJ1突变损害了心室多纤毛细胞的分化,从而导致通讯性脑积水。一些携带FOXJ1突变的患者可能继发脑脊液血流阻塞。杂合子FOXJ1突变破坏运动性纤毛结构和基底体排列,从而破坏脑脊液流动动力学,引起通讯性脑积水。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
期刊最新文献
Pesticide Exposure and Its Association with Parkinson's Disease: A Case-Control Analysis. Cognitive Impact of Neurotropic Pathogens: Investigating Molecular Mimicry through Computational Methods. Genetic Variability in Oxidative Stress, Inflammatory, and Neurodevelopmental Pathways: Impact on the Susceptibility and Course of Spinal Muscular Atrophy. Metformin Mitigates Trimethyltin-Induced Cognition Impairment and Hippocampal Neurodegeneration. Can Environmental Enrichment Modulate Epigenetic Processes in the Central Nervous System Under Adverse Environmental Conditions? A Systematic Review.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1