Delineating the role of the notochord during intervertebral disc development

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Intervertebral discs form the soft connective tissue joints of the spine required for spinal stabilization, load bearing, and movement. The central part of the disc, the nucleus pulposus, plays a key role in the physiological function of the intervertebral disc, however the developmental origin of its cells and the role of the notochord in its formation and maintenance are unknown. The loss of notochord cells from the intervertebral disc has been correlated with aging and degeneration, suggesting that the notochord plays an important role in this tissue. Cell-based strategies for intervertebral disc tissue engineering require a better understanding of the role of the notochord. The objective of these studies is to determine the role of notochord cells at specific stages of intervertebral disc development to determine if they act as stem cells in the nucleus pulposus. To trace notochord cells in the embryo and isolate them from distinct stages of spine development, we have generated a genetically engineered mouse in which notochord cells are marked by the expression of reporter genes. These studies will give us a better understanding of intervertebral disc formation by establishing the developmental origin of the nucleus pulposus and by better describing the properties of notochord cells in the intervertebral disc. Deciphering the factors that control intervertebral disc development may suggest strategies for the tissue engineering of these structures.