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

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...

Full description

Saved in:
Bibliographic Details
Published in:Histochemistry and cell biology 2018, Vol.149 (1), p.61-73
Main Authors: Li, Xuzhao, Xie, Jiongfang, Hei, Maofang, Tang, Jianli, Wang, Yanqing, Förster, Eckart, Zhao, Shanting
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Carbon-Nitrogen Ligases - genetics
Carbon-Nitrogen Ligases - metabolism
Cell Biology
Cell Cycle
Cell migration
Cell Proliferation
Cerebral Cortex - cytology
Cerebral Cortex - enzymology
Cortex
CTP synthase
Cytoplasm - enzymology
Developmental Biology
Electroporation
Embryos
Female
Mice
Mice, Inbred Strains
Neurogenesis - genetics
Neurons - enzymology
Optic lobe
Original Paper
Pregnancy
Progenitor cells
Prokaryotes
Stem cell transplantation
Stem cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0948-6143
1432-119X
DOI:10.1007/s00418-017-1612-2