How a single protein in non-neuronal cells controls brain development

September 23, 2020

Tsukuba, Japan - Normal brain development requires a precise interplay between neuronal and non-neuronal (also called glial) cells. In a new study, researchers from the University of Tsukuba revealed how the loss of protein arginine methyltransferase (PRMT) 1 causes disruptions in glial cells and affects proper brain development.

PRMTs modify specific amino acids of other proteins regulating key cellular functions, such as survival, proliferation and development. Of the many members of the PRMT family that have been identified to date, PRMT1 is one of the most common and controls tissue development and lifespan, as well as stress responses. Because total knockout of PRMT1, i.e., the loss of the protein in all tissues during development, results in failure of embryonic development, recently tissue-specific knockout of PRMT1 has been under increasing scrutiny, in an effort to understand how PRMT1 contributes to tissue development and function.

"We previously discovered that PRMT1 is critical for the function of one type of glial cell, oligodendrocytes, during brain development," says corresponding author of the study Professor Akiyoshi Fukamizu. "The goal of this study was to understand how other glial cells may contribute to the hypomyelination phenotype we observe in PRMT1 conditional knockout mice."

To achieve their goal, the researchers used the same mouse model as in their previous study, in which PRMT1 was knocked out in neural stem cells (NSCs) and cells that are derived from NSCs. These include oligodendrocytes and astrocytes, but not microglia, all of which are important glial cell types in the brain. The researchers performed RNA-sequencing of the outer region of the brain, called the cortex, where these cells reside in neonatal PRMT1 knockout mice. By doing so, they were able to survey changes in gene expression in the brain of mice lacking PRMT1. Interestingly, the researchers found increased expression of genes regulating inflammation, pointing towards the involvement of astrocytes and microglia. Looking closer at markers of inflammation, the researchers found that among a panel of inflammation markers the expression of Interleukin-6 in particular was significantly increased in PRMT1 knockout mice.

The researchers next asked how there is increased inflammation in the brain of neonatal mice lacking PRMT1 and looked closer at astrocytes and microglia. By assaying the brains for markers of astrocytes and microglia, they found signs of severe ongoing inflammation: massive astrogliosis, which is an increase in astrocyte numbers, and an increase in the number of microglia. The latter is particularly intriguing because microglia are not derived from NSCs and hence showed normal expression of PRMT1.

"These are striking results that show how a single protein controls such essential developmental processes in the brain. Our results provide a novel insight into the molecular control of brain development," says first author of the study Assistant Professor Misuzu Hashimoto (Gifu University).
-end-


University of Tsukuba

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.