In mice, researchers map a switch in early brain development

In Melbourne, researchers at the Murdoch Children’s Research Institute followed a developmental switch in genetically engineered mice lacking DLX1 and DLX2, two genes involved in how brain cells form, move and survive. By tracking thousands of genes, the team uncovered the DLX/Notch axis, a genetic signaling pathway that helps control when neural cells specialize.

That timing is the point. Before birth, brain cells must receive the right instructions at the right moment so they can move to the correct place and develop properly. The researchers found that DLX2 acts like a traffic controller: it helps young cells become neurons at the right time while holding back premature development into specialized support cells that help neurons function.

When DLX1 and DLX2 were removed, the cells developed differently and appeared in different locations in the brain. The team also identified previously unknown subregions of the developing forebrain, showing how a cell’s location is tied to the way it grows. The study was led by MCRI and published in Nature Communications.

The connection to disease is a research lead, not a treatment result. Pediatric high-grade gliomas, aggressive brain and spinal cord tumors in children and adolescents, are believed to develop when neural stem cells unexpectedly stop maturing. MCRI neuro-oncology leader David Eisenstat said the findings would inform future research into childhood brain tumors and neurodevelopmental disorders. The work described here used mice and focused on normal brain development; it does not report a human study or clinical benefit.

Concretely, the immediate value is for researchers: they now have a clearer set of molecular events to investigate in childhood tumors and neurodevelopmental disorders, including when cells change fate and where that change occurs. For children and families, these mouse findings do not yet alter diagnosis or treatment. MCRI presents them as groundwork for future efforts to improve treatment options.