Delineating the role of the notochord during intervertebral disc development

椎间盘形成脊柱的软结缔组织关节，是脊柱稳定、承载和运动所必需的。髓核是椎间盘的中心部分，在椎间盘的生理功能中起着关键作用，但其细胞的发育来源以及脊索在其形成和维持中的作用尚不清楚。腰椎间盘脊索细胞的丢失与衰老和退变有关，提示脊索在这一组织中起着重要作用。以细胞为基础的椎间盘组织工程策略需要更好地了解脊索的作用。这些研究的目的是确定脊索细胞在椎间盘发育的特定阶段的作用，以确定它们是否作为髓核中的干细胞。为了追踪胚胎中的脊索细胞，并将它们从脊柱发育的不同阶段分离出来，我们产生了一种基因工程小鼠，在其中脊索细胞通过报告基因的表达进行标记。这些研究将通过建立髓核的发育起源和更好地描述椎间盘中脊索细胞的特性，使我们对椎间盘的形成有更好的了解。破译控制椎间盘发育的因素可能会为这些结构的组织工程提供策略。

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.