West LA Times

Researchers at UCLA have identified a new function for the protein netrin1 in spinal cord development. Known for its role in guiding nerve fibers, netrin1 also limits bone morphogenetic protein (BMP) signaling to specific regions of the spinal cord. This finding is significant because BMP signaling must be confined to the dorsal region for proper sensory neuron development.

The study, published in Cell Reports, was led by Samantha Butler, a professor of neurobiology at the David Geffen School of Medicine. "This is a story of scientific curiosity — of discovering something odd and trying to understand why it happened," said Butler. The research highlights netrin1 as both an organizer of early spinal cord development and a guide for nerve fiber growth.

Sandy Alvarez, a graduate student and first author of the study, emphasized the importance of regional specificity: "Without netrin1’s regulation, we would likely see a disorganized neural network."

In previous research from 2017, Butler's team challenged existing beliefs about axon growth during embryonic development. They found that netrin1 acts more like an adhesive surface rather than as a distant cue. This discovery led them to further investigate netrin1's functions using experiments with chicken and mouse embryos.

Alvarez noted that initially she thought her experiments had failed when axons disappeared after introducing traceable netrin1 into developing spinal cords. However, repeated results showed that netrin1 repressed BMP activity.

Further analysis revealed that netrin1 indirectly inhibits BMP activity by controlling RNA translation. "Netrin1 is the most powerful architect of neuronal circuits that I have ever worked with," Butler stated.

The findings suggest potential clinical applications for neural repair using netrin1-based therapies. Moreover, they could impact understanding of other systems where precise cell patterning is essential due to interactions between BMP and netrin1.

Other contributors to this research include Sandeep Gupta, Yesica Mercado-Ayon, Kaitlyn Honeychurch, Cristian Rodriguez, and Riki Kawaguchi. Funding came from various sources including UCLA scholarships and grants from the National Institutes of Health.