期刊
CELL REPORTS
卷 19, 期 1, 页码 50-59出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.03.047
关键词
-
类别
资金
- Ministry of Innovation Science and Research of North Rhine-Westphalia (Junior Research Group)
- University of Bonn BONFOR Program
- ERA-NET NEURON, JTC 2015 Neurodevelopmental Disorders, STEM-MCD
- German Research Foundation [MU 3231/3-1]
Miller-Dieker syndrome (MDS) is caused by a heterozygous deletion of chromosome 17p13.3 involving the genes LIS1 and YWHAE (coding for 14.3.3 epsilon) and leads to malformations during cortical development. Here, we used patient-specific forebrain-type organoids to investigate pathological changes associated with MDS. Patient-derived organoids are significantly reduced in size, a change accompanied by a switch from symmetric to asymmetric cell division of ventricular zone radial glia cells (vRGCs). Alterations in microtubule network organization in vRGCs and a disruption of cortical niche architecture, including altered expression of cell adhesion molecules, are also observed. These phenotypic changes lead to a non-cell-autonomous disturbance of the N-cadherin/beta-catenin signaling axis. Reinstalling active beta-catenin signaling rescues division modes and ameliorates growth defects. Our data define the role of LIS1 and 14.3.3 epsilon in maintaining the cortical niche and highlight the utility of organoid-based systems for modeling complex cell-cell interactions in vitro.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据