Regulation and consequences of extracellular matrix remodelling protease activity in the developing zebrafish embryo.

活细胞分泌大量蛋白质，这些蛋白质构成了一种机械坚韧、生化复杂的细胞外基质(ECM)。正是这种基质赋予了大多数组织机械性能和许多生物学功能。为了使组织生长、愈合或以其他方式改变形状，细胞必须使用称为基质金属蛋白酶(MMPs)的酶来降解ECM。这项研究计划的目的是研究在斑马鱼胚胎发育过程中基质金属蛋白酶活性是如何被调节的，并更好地理解这一活动的生物学相关后果。斑马鱼胚胎在这项研究中很有用，因为与老鼠或其他哺乳动物的胚胎不同，斑马鱼胚胎在外部发育迅速，而且是透明的，使我们能够更容易地观察我们实验的效果。我们已经开发了新的技术，使我们能够看到MMPs的分布和激活模式，并确定它们在活胚胎中作用于哪些分子。这项研究不仅有助于我们更好地了解ECM重塑在胚胎发育过程中是如何调节的，它还应该为如何治疗由于基质金属蛋白酶活性调节不当而引起的病理变化提供一些见解，如关节炎、心脏病、中风和癌症。

Living cells secrete a number of proteins which make up a mechanically tough and biochemcially complex extracellular matrix (ECM). This matrix is what gives most tissues their mechanical properties and many of their biological functions. In order for tissues to grow, heal, or otherwise change shape, cells must degrade the ECM using enzymes called Matrix Metalloproteinases (MMPs). The objectives of this research proposal are to investigate how MMP activity is regulated during the embryonic development of the zebrafish embryo, and to better understand the biologically relevant consequences of that activity. The zebrafish embryo is useful in this study, because, unlike the embryos of mice or other mammals, the fish embryo develops externally, rapidly and it is transparent, allowing us to more easily observe the effects of our experiments. We have developed novel techniques that allow us to see the distribution and activation patterns of the MMPs, and also to determine what molecules they are acting on in the live embryo. Not only will this research help us better understand how ECM remodeling is regulated during embryonic development, it should also provide some insight into how to treat pathologies arising from the mis-regulation of MMP activity, such as arthritis, heart disease, stroke, and cancer.