MSX GENES IN WOUND HEALING AND REGENERATION

很少有文献记载人体器官能够 通过完全和完美地替换损坏的部件来应对伤害 零件。在适当的条件下，成人的手指是这样的 管风琴。数字由不同数量的不同单元格组成 构成手指的各种组织(例如，表皮，指甲， 甲床、真皮、脂肪、骨骼)，作为对截肢的反应，完美的 指尖的复制品，包括指甲和指纹 再生。这种再生反应是特定于级别的，并且仅发生 在甲床水平截肢后。另一个方面 手指再生的特点是伤口愈合时没有沉积。 疤痕组织，而截肢的伤口愈合恰好在 甲床(再生能力不强)会导致疤痕组织的形成。 因此，哺乳动物的断指是研究两者的一个模型系统。 器官再生和无疤痕伤口愈合。因此，它是 令人惊讶的是，人们对这方面的研究兴趣寥寥 显著的现象，尽管最常见的身体部位 受伤的是手，而在美国大约有1900人 在任何一年都会经历一位数的损失。 最好的手指再生模型是鼠标手指，并使用这个 我们已经启动了第一个数字的分子表征系统 形成和再生。数字重新生成与 伤口处有钉床组织，我们发现有两个同源异型盒- 包含基因(Msx1和Msx2)由甲床细胞表达，也 在再生过程中。最近，这两个基因都被敲除了 理查德·马斯博士的实验室。在与马斯博士的合作下，我建议 利用这些突变菌株来研究甲床和 MSX基因在控制手指再生和伤口愈合中的作用。 由于MSX突变小鼠无法存活到成年，我们将进行 这些实验是在子宫外异位发育的手指上进行的 在野生型胚胎上嫁接突变的指状幼体。具体的 目的包括L)刻画的再生诱导能力 甲床组织，2)甲床细胞在伤口中的作用 截肢后愈合，3)以出生后发育为特征， Msx1-/-突变小鼠MSX2-/-的再生能力和伤口愈合 Msx1-/-/msx2-/-双突变小鼠。

There are few documented instances in which human organs are able to respond to injury by complete and perfect replacement of the damaged parts. Under the appropriate conditions the adult digit is one such organ. The digit is composed of a diverse number of distinct cell types making up the various tissues of the digit (e.g. epidermis, nail, nailbed, dermis, adipose, bone), and in response to amputation, a perfect replica of the tip of the digit including the nail and fingerprint regenerates. This regeneration response is level-specific and only occurs following amputations at the level of the nailbed. An additional aspect of digit regeneration is that wound healing occurs without the deposition of scar tissue, whereas wound healing of amputations just proximal to the nailbed (regeneration-incompetent) results in scar tissue formation. Thus, digit amputation in mammals represents a model system to study both organ regeneration and scar-free wound healing. It is therefore surprising that there has been little interest in studying this remarkable phenomenon, despite the fact that the most frequent body part injured is the hand and that in the US approximately 19,00() people experience loss of a digit in any one year. The best model for digit regeneration is the mouse digit and using this system we have initiated the first molecular characterization of digit formation and regeneration. Digit regeneration is associated with the presence nailbed tissue at the wound and we show that two homeobox- containing genes (Msx1 and Msx2) are expressed by nailbed cells and also during regeneration. Recently both of these genes have been knockout in the lab of Dr. Richard Maas. In collaboration with Dr. Maas I propose to utilize these mutant strains to investigate the role of the nailbed and the Msx genes in the control of digit regeneration and wound healing. Because the Msx mutant mice do not survive to adulthood, we will conduct these experiments on digits that develop ectopically following exo-utero grafting of mutant digit rudiments onto wild type embryos. The specific aims include l) characterizing the regeneration-inducing capacity of nailbed tissue, 2) characterizing the role of nailbed cells in wound healing following amputation, 3) characterizing post-natal development, regenerative potential and wound healing of Msx1-/- mutant mice, Msx2-/- mutant mice, and Msx1-/-/Msx2-/-double mutant mice.