Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids  

作　　者：Peng Li Ting Zhang Ruo Wu Jun-Yu Zhang Yan Zhuo Shan-Gang Li Jiao-Jian Wang Wen-Ting Guo Zheng-Bo Wang Yong-Chang Chen 

机构地区：[1]State Key Laboratory of Primate Biomedical Research,Institute of Primate Translational Medicine,Kunming University of Science and Technology,Kunming,Yunnan 650500,China [2]Yunnan Key Laboratory of Primate Biomedical Research,Kunming,Yunnan 650500,China

出　　处：《Zoological Research》2024年第2期233-241,共9页动物学研究（英文）

基　　金：supported by the National Natural Science Foundation of China (81930121,82125008 to Y.C.C.);National Key Research and Development Program of China (2018YFA0107902 to Y.C.C.and 2018YFA0801403 to Z.B.W.);Major Basic Research Project of Science and Technology of Yunnan (202001BC070001 to Y.C.C.);Natural Science Foundation of Yunnan Province (202102AA100053 to Y.C.C.)。

摘　　要：Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure.Although folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain unpreventable.The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains unclear.Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate.To determine the role of SHROOM3 in early developmental morphogenesis,we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase.Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei.These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins,namely fibrous actin(F-actin),myosin II,and phospho-myosin light chain(PMLC),to the apical side of the neuroepithelial cells.Notably,these defects were not rescued by folate supplementation.RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis.In summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

关 键 词：Neural tube defects SHROOM3 NEUROEPITHELIAL ORGANOIDS Cynomolgus monkey 

分 类 号：R748[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]