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 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

作者机构：State Key Laboratory of Primate Biomedical ResearchInstitute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China Yunnan Key Laboratory of Primate Biomedical ResearchKunmingYunnan 650500China 

出 版 物：《Zoological Research》 (动物学研究（英文）)

年 卷 期：2024年第45卷第2期

页      面：233-241页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

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.) 

主　　题：Neural tube defects SHROOM3 Neuroepithelial Organoids Cynomolgus monkey 

摘      要：Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube *** folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain *** SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains *** tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural *** 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 *** of SHROOM3 resulted in shorter neuroepithelial cells and smaller *** 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 ***,these defects were not rescued by folate *** sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ *** summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.