Role of movo Genes in Hair Morphogenesis

哺乳动物毛囊是研究细胞增殖、分化和形态发生等基本细胞过程的良好系统。目前，人们对毛囊中调控毛发形成的分子途径知之甚少。毛发是一种在感觉、温度调节和社会互动中发挥重要作用的器官。小鼠卵子基因似乎是毛囊后期分化(即毛发形态发生)所必需的。因此，它们提供了一个有用的分子手柄，用来研究增殖的毛囊细胞如何分化为毛干高度特化的终末细胞。在这项研究中，将产生携带MoVo基因突变的小鼠，并用于分析毛发形成过程中发生的细胞和分子事件，以及这些事件是如何调控的。研究目的有三个：1.研究MoVo基因在小鼠发育和生理过程中的功能，特别是在毛发形态发生和表皮分化中的作用。毛发形态发生需要movo2的假设将通过产生和分析定向缺失movo2基因的小鼠来检验。假设movo1和movo2双基因敲除小鼠。对突变小鼠的分析将包括对表达movo2的组织进行系统观察和组织学研究，重点是毛发和表皮缺陷。将在突变小鼠身上检测形态和生化标记，以确定毛发和表皮缺陷的确切性质。2.研究MoVo的作用机制：1.基因表达调控的孤立性？MoVo蛋白被认为是转录因子。MoVo下游的靶基因将被鉴定出来，并通过在体外和体内研究MoVo蛋白来调节它们。MoVo蛋白的转录调节活性也将被表征。3.研究MoVo功能的机制II.在细胞骨架和/或细胞黏附中可能的作用？MoVo基因在肌动蛋白细胞骨架重组和/或细胞黏附中具有额外功能的假设将通过a)检测MoVo过度表达或缺失对小鼠角质形成细胞细胞骨架/黏附的影响，以及b)在MoVo基因产物水平异常的敲除和转基因小鼠中检测MoVo过度表达或缺失对这些细胞过程的影响。

Mammalian hair follicle is an excellent system to study essential cellular processes such as proliferation, differentiation, and morphogenesis. At the present time, little is known about the molecular pathways that operate in hair follicles to govern the formation of hair, an organ that plays important roles in sensation, temperature regulation, and social interaction. The mouse ovo genes appear to be required for the late-stage differentiation with the hair follicles (i.e., hair morphogenesis). Therefore, they provide a useful molecular handle with which to study how proliferative hair follicle cells differentiate into the highly specialized terminal cells of the hair shaft. In this proposal, mice carrying mutations in the movo genes will be generated, and used to dissect the cellular and molecular events that occur during the process of hair formation, and how these events are regulated. There are three specific aims: 1. Characterizing the functions of movo genes in mouse development and physiology, particularly in hair morphogenesis and epidermal differentiation. The hypothesis that movo2 is required for hair morphogenesis will be tested by generating and analyzing mice with a targeted deletion of the movo2 gene. The hypothesis that movo1 and movo2 double knockout mice. Analysis of mutant mice will include a systematic observation and histological studies of tissues that express movo2, with an emphasis on hair and epidermal defects. Morphological and biochemical markers will be examined in the mutant mice to pinpoint the exact nature of the defects in hair and epidermis. 2. Investigating the mechanisms of movo functions I: a lone in regulating gene expression? mOvo proteins are thought to act as transcription factors. The mOvo downstream target genes will be identified and their regulation by the mOvo proteins studied both in vitro and in vivo. The transcriptional regulatory activities of the mOvo proteins will also be characterized. 3. Investigating the mechanisms of movo functions II. a possible role in cytoskeleton and/or cell adhesion? The hypothesis that movo genes carry an additional function in actin cytoskeleton reorganization and/or cell adhesion will be tested by a)examining the effect of movo over-expression or deletion on cytoskeleton/adhesion in mouse keratinocytes, and b) examining the effect of movo over-expression or deletion on these cellular processes in the knockout and transgenic mice with abnormal levels of movo gene products.