Vertebrae, the Spine, Cells, and a Clock: Understanding Spinal Defects

In an advance on their initial discovery from 20 years ago, researchers from Harvard Medical School report new insight into the segmentation clock, the mechanism by which vertebrae are successively formed to create the spine. The new discoveries, involving the location of the clock and its mechanism of operation, resulted from work with mouse cells used to create a stable version of the clock in a petri dish. The team believes the additional information could be useful in improving our understanding of scoliosis and other spinal defects in humans. Their work was published last week in the journal Cell.

The team, led by Olivier Pourquie, PhD, professor of genetics at Harvard Medical School, reports that the segmentation clock is dormant in embryonic cells that form the vertebrae, and is activated and regulated by 2 signals, Notch and Yap, that are communicated to the cells. Notch triggers cellular oscillations that initiate the process of vertebrae formation, while Yap determines the amount of Notch needed to activate the segmentation clock. In an important discovery, the team was able to intervene in this process, both physically by moving the cells, and chemically, with an agent that blocked Yap. Dr. Pourquie commented, “For many years, we have been trying to understand the clockwork underlying these oscillations. Now we have a great theoretical framework to understand what generates them and to help us make and test more hypotheses.”

Read a news story about the findings.

The journal abstract may be read here.