Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells,Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice  

作　　者：Xue Li Shimin Zou Xiaomeng Tu Shishuai Hao Tian Jiang Jie-Guang Chen 

机构地区：[1]School of Ophthalmology and Optometry and Eye Hospital,Wenzhou Medical University,Wenzhou 325027,China [2]State Key Laboratory of Optometry,Ophthalmology and Vision Science,and Zhejiang Provincial Key Laboratory of Optometry and Ophthalmology,Wenzhou 325027,China [3]Research Center for Translational Medicine,the Afliated Wenling Hospital of Wenzhou Medical University,Wenling 317500,China

出　　处：《Neuroscience Bulletin》2023年第7期1131-1145,共15页神经科学通报（英文版）

基　　金：supported by the Wenzhou Municipal Science and Technology Bureau(Y20210901);the Natural Science Foundation of Zhejiang Province(LQ20H090001);the Scientific Research Fund of Wenling Science and Technology Bureau(2018C320001).

摘　　要：Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders(NDDs)that exhibit delayed speech development,intellectual disability,and congenital abnormalities.The etiology of NDDs is unclear.Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells(RGCs),respectively,in the mouse neocortex during early gestation.Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone(VZ).Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ.The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs.The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions,the loss of which leads to periventricular heterotopias.We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.

关 键 词：NEUROGENESIS Radial migration Radial glial cell Ventricular zone N-CADHERIN 

分 类 号：Q421[生物学—神经生物学]