You are here

Wake-up call for neural stem cells

SINGAPORE, February 2021 — Researchers studying an 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.

Pr-set7 is an enzyme involved in maintaining genome stability, DNA repair and cell cycle regulation, as well as turning various genes on or off. This protein, which goes by a few different names, has remained largely unchanged as species have evolved. Hongyan Wang, Ph.D., a professor and deputy director at Duke-NUS’ Neuroscience and Behavioural Disorders Programme, and her colleagues set out to understand the protein’s function during brain development.

“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 Prof. Wang. “Our study is the first to show that Pr-set7 promotes neural stem cell reactivation and, therefore, plays an important role in brain development.”

Neural stem cells normally oscillate between states of quiescence and proliferation. Maintaining an equilibrium between the two is very important. Most neural stem cells are quiescent in adult mammalian brains. They are reactivated to generate new neurons in response to stimuli, such as injury, the presence of nutrients or exercise.

However, neural stem cells gradually lose their capacity to proliferate with age and in response to stress and anxiety. 

Prof. 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 signaling 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 Prof Wang.

 

Quiescent neural stem cells in the fruit fly larval brain.  When activated, they can generate new neurons. The nucleus of quiescent neural stem cells is labelled by a marker of neural stem cells called Deadpan, in magenta. The cell outline is marked in green. Image courtesy of Wang Hongyan.

Learn more:
https://www.duke-nus.edu.sg/about/media/media-releases/media-releases/wake-up-call-for-neural-stem-cells
DOI: 10.15252/embr.202050994