Could an active enzyme in fruit fly larvae play a critical role in stem cell research? A new study has revealed some surprisingly encouraging results.
Singapore researchers found that an enzyme in fruit fly larvae plays a key function in triggering brain stem cells from their dormant quiescent state so they can reproduce and generate new neurons. The study was conducted by Duke-NUS Medical School, Singapore and published EMBO Reports. The research may illuminate how certain neurodevelopmental disorders such as autism and microcephaly occur.
The researchers studied Pr-set7, which is an enzyme that turns various genes on and off. The enzyme is involved in maintaining cell cycle regulation, DNA repair, and genome stability. The protein has remained largely unchanged throughout evolution.
“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 Hongyan Wang, Ph.D., a professor and deputy director at Duke-NUS’ Neuroscience and Behavioral Disorders Programme. “Our study is the first to show that Pr-set7 promotes neural stem cell reactivation and, therefore, plays an important role in brain development.”
The Study in a Nutshell
“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.”
A New Understanding of Neurodevelopmental Disorders & Treatment
The study broadens scientific awareness of the roles of its mammalian counterpart in neural stem cell development as well as associated neurodevelopmental disorders.
“With this latest study, Professor Wang’s fundamental research in neuroscience has yielded valuable insights into several neurodevelopmental disorders; insights that have the potential to improve the way we care for people with such disorders,” comments Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS.