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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. Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids. Zoological Research, 2024, 45(2): 233-241. doi: 10.24272/j.issn.2095-8137.2023.190
Citation: 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. Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids. Zoological Research, 2024, 45(2): 233-241. doi: 10.24272/j.issn.2095-8137.2023.190

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

doi: 10.24272/j.issn.2095-8137.2023.190
RNA sequencing data have been deposited in the NCBI (PRJNA1029382), China National Center for Bioinformation (PRJCA020595), and Science Data Bank databases (DOI:10.57760/sciencedb.j00139.00075).
Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
Y.C.C., P.L., and Z.B.W. conceived the project. T.Z. and R.W. established the ES cell lines. J.Y.Z. performed the RNA-seq data analysis. P.L., R.W., and Y.Z. performed the experiments. S.G.L. and J.J.W. conceptualized the research and provided critical feedback. P.L., Y.C,C., and W.T.G. wrote the manuscript. All authors read and approved the final version of the manuscript.
#Authors contributed equally to this work
Funds:  This work was 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.)
More Information
  • 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.
  • RNA sequencing data have been deposited in the NCBI (PRJNA1029382), China National Center for Bioinformation (PRJCA020595), and Science Data Bank databases (DOI:10.57760/sciencedb.j00139.00075).
    Supplementary data to this article can be found online.
    The authors declare that they have no competing interests.
    Y.C.C., P.L., and Z.B.W. conceived the project. T.Z. and R.W. established the ES cell lines. J.Y.Z. performed the RNA-seq data analysis. P.L., R.W., and Y.Z. performed the experiments. S.G.L. and J.J.W. conceptualized the research and provided critical feedback. P.L., Y.C,C., and W.T.G. wrote the manuscript. All authors read and approved the final version of the manuscript.
    #Authors contributed equally to this work
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