首页|Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells,Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice
Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells,Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice
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Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders(NDDs)that exhibit delayed speech development,intel-lectual disability,and congenital abnormalities.The etiol-ogy 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 neo-cortex during early gestation.Knockdown or dominant-neg-ative 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 differ-entiation 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 hypoth-esize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.
School of Ophthalmology and Optometry and Eye Hospital,Wenzhou Medical University,Wenzhou 325027,China
State Key Laboratory of Optometry,Ophthalmology and Vision Science,and Zhejiang Provincial Key Laboratory of Optometry and Ophthalmology,Wenzhou 325027,China
Research Center for Translational Medicine,the Affiliated Wenling Hospital of Wenzhou Medical University,Wenling 317500,China
Wenzhou Municipal Science and Technology BureauNatural Science Foundation of Zhejiang ProvinceScientific Research Fund of Wenling Science and Technology Bureau
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