The Duke-NUS and NNI team showed that miR-128 targets a protein called PCM1 that is critical to the cell division of neural precursor cells (NPCs). NPCs during early brain development have two fates - they either stay as NPCs and undergo self-renewal or become neurons through differentiation. The dysfunctional regulation of PCM1 by misregulated miR-128 impairs brain development, which may underlie brain size changes in people with ASDs.
“For the first time, we have managed to show that miR-128 is a mechanism that regulates early neuronal behaviour during brain development,” said Asst Prof Je, from the Neuroscience and Behavioural Disorders (NBD) Programme at Duke-NUS. “Targeting this mechanism may be the answer to diagnose and treat ASDs that are caused by abnormal brain development."
Asst Prof Li, from the Neural Stem Cells Laboratory at NNI, added, “This important study suggests a link between a key neurological disease gene and regulation of microRNAs in the brain. However, we are just starting to understand how misregulated miR-128 expression can cause our brain activities to go wrong, and much more work needs to be done.”
In a separate study which is not yet published, this team with Professor Steve Rozen, from the NBD Programme at Duke-NUS, identified many new mutations in the PCM1 gene from ASD patients from next-generation sequencing. Future work to correlate these mutations with functional consequences in brain development should not only increase the understanding of how autism is caused, but also enable a more accurate diagnosis of autism and other ASDs.
Study authors include first authors, Dr Zhang Wei, a Post-Doctoral Fellow from the NNI and MD/PhD student Paul Kim from Duke-NUS. Research is supported by the A*STAR Translational Clinical Research Partnership Award.