Researchers Shed New Light On A Key Player in Brain Development

    Researchers at The University of Texas Medical Branch at Galveston have shed light on how the developing brain ensures that connections between brain cells reach their intended destination but that they are also maintained during life-span.  The team reported its findings (“The glycosylation pathway is required for the secretion of Slit and for the maintenance of the Slit receptor Robo on axons”) in Science Signalling.

    The brain contains regions that serve specific functions such as interpreting sensory information, controlling bodily movement or formation of memory, and so on. In order for regions to interact with one another to perform complex tasks, the brain has a web of interconnecting pathways.

    Krishna M. Bhat, Ph.D., UTMB professor in the department of neuroscience and cell biology, and his colleagues demonstrated that a protein called Slit is necessary for maintaining the interconnecting pathways in the nervous system. Without Slit, the intended pathways drift off course.

    The study found that Slit keeps brain cells on their paths in partnership with receptor proteins called Robo, according to Dr. Bhat. The researchers also discovered that that Slit-Robo signaling is controlled by an enzyme called Mummy, which modifies Slit such that it could be secreted outside the cell where it is made. Slit also maintains correct amounts and spatial distribution of Robo during early and late nervous system development.

    “We showed that the enzyme Mummy (Mmy) controlled Slit-Robo signaling through mechanisms that affected both the ligand and the receptor,” wrote the investigators. “Mmy was required for the glycosylation of Slit, which was essential for Slit secretion. Mmy was also required for maintaining the abundance and spatial distribution of Robo through an indirect mechanism that was independent of Slit secretion.”

    “Although Slit-Robo signaling is intensely studied, the emphasis has always been on understanding the events controlling the beginning of the process of guiding developing brain circuits to their destinations,” explained Dr. Bhat. “Here, we show that Slit-Robo signaling is required not only at the initial stages of brain circuitry guidance but also later for maintaining those networks of circuits. This has implications for loss of cognition and other brain functions as we age or in many neuro-diseases.”

    The study was conducted using Drosophila, as the control of brain circuitry pathfinding mechanisms in this animal model is similar to what happens during human development.