Normal brain development requires precise interactions between neurons and non-neurons (also known as glia) cells.In a new study, researchers at the University of Tsukuba have revealed how the loss of the protein arginine methyltransferase (PRMT) 1 causes the breakdown of glial cells and affects normal brain development.

PRMT modifies specific amino acids in other proteins to regulate key cellular functions such as survival, proliferation, and development.Of the many members of the PRMT family identified so far, PRMT1 is one of the most common, controlling tissue development and longevity as well as stress response.Because complete knockout of PRMT1 (the loss of proteins in all tissues during development) leads to embryonic development failure, tissue-specific knockout of PRMT1 has recently been studied with increasing rigor to understand how PRMT1 promotes tissue development.

"We have previously found that PRMT1 is essential for the function of a type of glial cell called oligodrocytes during brain development," said Professor Shum Shu-shen Min-ji, corresponding author of the study."The purpose of this study was to understand how other glial cells that we observed in PRMT1 conditional knockout mice might cause myelin dysplasia."

To achieve their goal, the researchers used the same mouse model as previous studies, in which PRMT1 was knocked out into neural stem cells (NSCS) and cells derived from NSCS.These include oligodendrocytes and astrocytes, but not microglia cells, which are important types of glial cells in the brain.The researchers sequenced RNA from an external region of the brain called the cortex, which is located in mice that have been genetically knocked out with the PRMT1 gene.By doing so, they were able to investigate changes in gene expression in the brains of mice that lacked PRMT1.Interestingly, the researchers found increased expression of genes that regulate inflammation, indicating the involvement of astrocytes and microglia.Looking closely at inflammatory markers, the researchers found that expression of il-6, in particular, increased significantly in PRMT1 knockout mice in a set of inflammatory markers.

Next, the researchers asked newborn mice that lacked PRMT1 and looked closely at how inflammation increased in the brains of astrocytes and microglias.By analyzing markers of astrocytes and microglia in the brain, they found signs of severe persistent inflammation: lots of astrocytes, lots of astrocytes, lots of microglia.

"These results suggest that PRMT1 regulates important brain development processes," said lead author and assistant professor Misuzu Hashimoto.Our results provide novel insights into the molecular control of brain development."