2019 Fiscal Year Annual Research Report
Identification and characterization of PLA2 enzyme required for sensory nervous system development
| Project/Area Number |
17K14970
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
GUY ADAM・TSUDA 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (30634779)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | Lipid Biology / Neuroscience / Cell Biology / Molecular Biology |
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| Outline of Annual Research Achievements |
Discovery of radial glial secreted phospholipase A2 (sPLA2) isoform V that modulates LysoPtdGlc/GPR55 signaling in embryonic spinal cord:
My earlier research found that spinal cord radial glia specifically express the membrane phospholipid phosphatidylglucoside (PtdGlc) during development. In this current project I discovered that radial glial sPLA2 hydrolyses membrane PtdGlc to release the water-soluble lysolipid lysophosphatidylglucoside (LysoPtdGlc) into the extracellular space. After extracting and culturing radial glia cells to compare with total spinal cord tissue, I used digital PCR to achieve absolute quantification of mRNA expression levels of all ten isoforms of sPLA2 in spinal cord. I discovered that only one isoform, sPLA2 V (gene name: pla2g5) is specifically expressed by radial glia and not by other cells. In contrast, sPLA2 X (gene name: pla2g10) is expressed by non-glial spinal cord cells. Since I previously demonstrated that glial LysoPtdGlc signalling at GPR55 is an in vivo axon guidance mechanism, I hypothesised that spinal cord lacking sPLA2 V may have a phenotype similar to GPR55 loss-of-function. Using a knockout mouse line, I discovered that embryos with genetic deletion of sPLA2 V (pla2g5-/-) enzyme have a defect in nociceptive axon (identified by TrkA expression) tract formation, defined by an abnormal expansion into the medial spinal cord from which they are absent in wildtype. In conclusion, presence of radial glial sPLA2 V activity modulates the LysoPtdGlc/GPR55 signalling mechanism that is required for spinal cord sensory axon tract development.
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