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High level of CTP synthase induces formation of cytoophidia in cortical neurons and impairs corticogenesis

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Abstract

De novo synthesis of the nucleotide CTP is catalyzed by the essential pyrimidine biosynthesis enzyme CTP synthase (CTPs), which forms large-scale filamentous structures consisting of CTPs termed cytoophidia in prokaryotes and in eukaryotes. Recent studies have shown that cytoophidia are abundant in neuroepithelial stem cells in Drosophila optic lobes and that overexpression of CTPs impairs optic lobe development. Whether CTPs and cytoophidia also play a role in the development of the mammalian cortex remains elusive. Here, we show that overexpression of CTPs by in utero electroporation in the embryonic mouse brain induces formation of cytoophidia in developing cortical neurons and impairs neuronal migration. In addition, the increase of cytoophidia accelerates neuronal differentiation and inhibits neural progenitor cell proliferation by reducing their mitotic activity. Furthermore, we discovered that the cytoophidia diffused during the early G1-phase of the cell cycle. Together, our findings show, for the first time, that CTPs play a significant role in the development of the mammalian cortex.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31572477). We thank the Life Science Research Core Services (LSRCS) in Northwest A&F University for supplying the Leica TCS SP8.

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Author notes

  1. Xuzhao Li and Jiongfang Xie have contributed equally to this work.

Authors and Affiliations

  1. College of Veterinary Medicine, Northwest A&F University, No. 22 Xinong Road, Yangling, 712100, Shaanxi, China

    Xuzhao Li, Jiongfang Xie, Maofang Hei, Jianli Tang & Shanting Zhao

  2. Life Science Research Core Services (LSRCS), Northwest A&F University, Yangling, 712100, Shaanxi, China

    Yanqing Wang

  3. Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Universitätsstr 150, 44801, Bochum, Germany

    Eckart Förster

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  1. Xuzhao Li
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Correspondence to Shanting Zhao.

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Li, X., Xie, J., Hei, M. et al. High level of CTP synthase induces formation of cytoophidia in cortical neurons and impairs corticogenesis. Histochem Cell Biol 149, 61–73 (2018). https://doi.org/10.1007/s00418-017-1612-2

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