Regulation of matrix metalloproteinase activity during zebrafish morphogenesis

活细胞分泌一种坚硬的蛋白质基质，构成细胞外基质（ECM），这种基质赋予了大多数组织机械特性。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。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。我们已经开发了一种新技术，使我们能够可视化完整斑马鱼胚胎中MMPs的活性，我们正在使用这种技术更好地了解胚胎发育过程中ECM重塑是如何被调节的。这种理解将为我们提供一些关于如何治疗由MMP活动失调引起的病理的见解，如关节炎、心脏病、中风和癌症。

Living cells secrete a matrix of tough proteins which make up an extracellular matrix (ECM), and this matrix is what gives most tissues their mechanical properties.  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.  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 a novel technique that allows us to visualize the activity of the MMPs in the intact zebrafish embryo, and we are using this technique to better understand how ECM remodeling is regulated during embryonic development.  This understanding will provide us with some insight into how to treat pathologies arising from the mis-regulation of MMP activity, such as arthritis, heart disease, stroke, and cancer.