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

活细胞分泌许多蛋白质，这些蛋白质构成了机械坚韧和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特性和许多生物功能。为了使组织生长、愈合或改变形状，细胞必须使用一种叫做基质金属蛋白酶（MMPs）的酶来降解ECM。本研究计划的目的是研究斑马鱼胚胎发育过程中MMP活性是如何调节的，并更好地了解该活性的生物学相关后果。斑马鱼胚胎在这项研究中是有用的，因为与小鼠或其他哺乳动物的胚胎不同，鱼胚胎在外部发育，快速且透明，使我们更容易观察我们的实验效果。我们已经开发出新的技术，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。这项研究不仅可以帮助我们更好地了解胚胎发育过程中ECM重塑是如何被调节的，还可以为如何治疗由MMP活性失调引起的疾病，如关节炎、心脏病、中风和癌症提供一些见解。

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.