Pr-set7 Enzyme Activates Dormant Neural Stem Cells

Researchers studying the Pr‐set7/SETD8 enzyme in fruit fly larvae have found that it plays an important role in waking up brain stem cells from their dormant quiescent state, enabling them to proliferate and generate new neurons. Published in EMBO Reports, the study by Duke-NUS Medical School, Singapore, could help clarify how some neurodevelopmental disorders such as autism and microcephaly occur.

"Genetic variants of the human version of Pr-set7 are associated with neurodevelopmental disorders, with typical symptoms including intellectual disability, seizures and developmental delay," explained lead researcher Wang Hongyan. "Our study is the first to show that Pr-set7 promotes neural stem cell reactivation and, therefore, plays an important role in brain development."

Wang and her colleagues studied what happened when the gene coding for Pr-set7 is turned off in larval fruit fly brains. They found it caused a delay in the reactivation of neural stem cells from their quiescent state. To reactivate neural stem cells, Pr-set7 needs to turn on at least two genes: cyclin-dependent kinase 1 (cdk1) and earthbound 1 (Ebd1). The scientists found that overexpressing the proteins coded by these genes led to the reactivation of neural stem cells even when the Pr-set7 gene was turned off. These findings show that Pr-set7 binds to the cdk1 and Ebd1 genes to activate a signalling pathway that reactivates neural stem cells from their quiescent state.

"Since Pr-set7 is conserved across species, our findings could contribute to the understanding of the roles of its mammalian counterpart in neural stem cell proliferation and its associated neurodevelopmental disorders," said Wang. The scientists are now extrapolating this study to understand the roles of the mammalian and human forms of Pr-set7, called SETD8 and KMT5A respectively, in brain development.