Unique mechanism of spinal disc repair discovered
Researchers have discovered a unique repair mechanism of spinal discs in zebrafish which could provide insight into why spinal discs of longer-lived organisms, such as humans, degenerate with age.
Researchers from Duke University (NC, USA) have discovered a unique repair mechanism for spinal discs in zebrafish. The repair mechanism involves epithelial sheath cells turning into vacuolated cells and could provide insight into why spinal discs in humans degenerate. The research was recently published in Current Biology.
The notochord of zebrafish consists of a sheath of epithelial cells surrounding a collection of giant fluid-filled or “vacuolated” cells. During the development of these fish the vacuolated cells rarely pop despite being under great mechanical stress. Recent research has suggested that tiny pouches that form in the plasma membrane of these cells, known as caveolae, can provide a buffer against stretching or swelling.
To test if caveolae protected cells vacuoles from bursting researchers generated mutants of three caveolar genes in zebrafish. The researchers found that their vacuolated cells started to break up and caused serial lesions on the notochord. Despite these lesions the mature spine formed normally.
To test why the spine still formed normally researchers marked the vacuolated cells green and the surrounding epithelial sheath cells red, then filmed the fish shortly after they hatched and started swimming. At first, they could see an occasional vacuolated cell break and spill its contents like a water balloon. However, over the course of fifteen hours, that noticed that a nearby epithelial sheath cell would move in, crawl over the detritus of the collapsed cell and morph into a new vacuolated cell. It was also discovered that the release of nucleotides was the key to this happening.
“These cells, which reside in the discs of both zebrafish and man, seem capable of controlling their own repair and regeneration,” commented study senior author and assistant professor of cell biology Michel Bagnat (Duke University). “Perhaps it is a continuous release of nucleotides that is important for keeping the disc in good shape.”
The study may offer insight not only into the development of back and neck pain, but also into the origins of cancer. Their data suggests that chordomas, rare and aggressive notochord cell tumors, may begin when epithelial sheath cells leave the notochord and invade the skull and other tissue.
Sources: Garcia J, Bagwell J, Njaine B et al. Sheath Cell Invasion and Trans-differentiation Repair Mechanical Damage Caused by Loss of Caveolae in the Zebrafish Notochord. Curr. Biol. pii: S0960-9822(17)30571-7 (2017) (Epub ahead of print); https://today.duke.edu/2017/06...