Melbourne researchers have uncovered a critical signalling pathway that controls the timing of brain development, shedding new light on how neurodevelopmental disorders may develop.
The research, led by Murdoch Children's Research Institute (MCRI) and published in Nature Communications, has revealed the genetic processes that shape brain development and what can happen when they become disrupted. Some paediatric high-grade gliomas (pHGGs), an aggressive type of brain and spinal cord tumour in children and adolescents, are believed to develop when neural stem cells stop maturing unexpectedly.
MCRI Dr Ryan Leung said the findings help to explain how the brain builds its complex network of cells during development.
"The brain develops rapidly before birth, and cells must receive the right instructions at the right time in order to move to the correct place to develop properly," he said. "We have uncovered new clues about one of the brain's most important developmental switches."
Using cutting-edge genomic techniques, the researchers tracked how thousands of genes shape the developing brain. They used mice genetically engineered to lack DLX1 and DLX2, two key genes that control how cells form, move, and survive in the brain.
"We discovered that the gene DLX2 acts like a traffic controller during early brain development, ensuring young brain cells become neurons at the right time while preventing them from prematurely developing into specialised support cells that help neurons function properly," Dr Leung said. "When these genes were removed, we saw changes in how these cells developed and where they were located in the brain. "The team also found previously unidentified subregions of the developing forebrain, revealing how the location of cells impacts the way they grow."
MCRI Neuro-oncology Group Leader Professor David Eisenstat said the findings would also inform future research into childhood brain cancers and neurodevelopmental disorders.
"While the research focused on normal brain development, it sheds light on the molecular pathways that control how brain cells develop and specialise," he said. "Many of these same pathways are known to be disrupted in childhood brain tumours, including high-grade gliomas, making them important areas for future research and ultimately around work into improving treatment options."
Researchers from the University of Melbourne, Monash University, The Royal Children's Hospital and the University of Alberta also contributed to the research.
Publication: Ryan Leung, Michael See, Ankita George, Patrick Barry, Kyle France, Natalie Charitakis, Mirana Ramialison, Maree Faux and David Eisenstat. 'The DLX/Notch axis is necessary for spatiotemporal regulation of neural cell fate,' Nature Communications. DOI: 10.1038/s41467-026-76838-0
*The content of this communication is the sole responsibility of MCRI and does not reflect the views of the NHMRC.
