MSX GENES IN WOUND HEALING AND REGENERATION

很少有记录表明人体器官能够 通过完整和完美地更换损坏的部件来应对损伤 零件.在适当的条件下，成人的手指就是这样一个手指。 器官.足趾由不同数量的不同细胞类型组成 构成手指的各种组织（例如表皮，指甲， 甲床，真皮，脂肪，骨），并在截肢反应，一个完美的 指尖的复制品，包括指甲和指纹 重生此再生响应是特定于级别的， 在甲床水平截肢后。另外的方面 指再生的关键是伤口愈合时 的疤痕组织，而伤口愈合截肢只是近端的 甲床（再生不全）导致疤痕组织形成。 因此，在哺乳动物中的趾截肢代表了一个模型系统，以研究两者 器官再生和无疤痕伤口愈合。因此 令人惊讶的是，人们对研究这一问题几乎没有兴趣。 这是一个值得注意的现象，尽管最常见的身体部位 受伤的是手，在美国大约有19，000人受伤， 任何一年中都会失去一个手指。 手指再生的最佳模型是老鼠的手指， 系统，我们已经启动了第一个数字的分子表征 形成和再生。足趾再生与 伤口处的甲床组织，我们发现两个同源异型盒- 含有基因（Msx 1和Msx 2）的细胞由甲床细胞表达， 在再生过程中。最近，这两个基因都被敲除， 理查德·马斯博士的实验室与马斯博士合作，我建议 利用这些突变株来研究甲床的作用， Msx基因在手指再生和伤口愈合的控制。 因为Msx突变小鼠不能存活到成年，我们将进行 这些实验是关于在子宫外出生后异位发育的手指的 将突变的趾雏形嫁接到野生型胚上。具体 目的包括l）表征再生诱导能力， 甲床组织，2）表征甲床细胞在伤口中的作用 截肢后愈合，3）表征产后发育， Msx 1-/-突变小鼠的再生潜力和伤口愈合，Msx 2-/- 突变小鼠和Msx 1-/-/Msx 2-/-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.