Role of movo Genes in Hair Morphogenesis

哺乳动物毛囊是研究细胞增殖、分化和形态发生等重要过程的理想系统。 目前，人们对毛囊中控制头发形成的分子途径知之甚少，头发是一种在感觉、温度调节和社会互动中起重要作用的器官。 小鼠卵细胞基因似乎是毛囊后期分化所需的（即，毛发形态发生）。因此，他们提供了一个有用的分子手柄，研究如何增殖毛囊细胞分化成高度专业化的毛干终末细胞。 在这项提议中，将产生携带movo基因突变的小鼠，并用于剖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节的。具体目标有三：1。描述movo基因在小鼠发育和生理学中的功能，特别是在毛发形态发生和表皮分化中的功能。 将通过产生和分析具有movo 2基因的靶向缺失的小鼠来测试movo 2是毛发形态发生所需的假设。 movo 1和movo 2双基因敲除小鼠的假说。 对突变小鼠的分析将包括对表达movo 2的组织的系统观察和组织学研究，重点是毛发和表皮缺陷。 将在突变小鼠中检查形态学和生物化学标记，以确定毛发和表皮缺陷的确切性质。 2. MOVO功能机制的研究I：一个调节基因表达的孤例？ mOvo蛋白被认为是转录因子。 将鉴定mOvo下游靶基因，并在体外和体内研究mOvo蛋白对其的调节。 还将表征mOvo蛋白的转录调节活性。 3. Movo功能机制研究2。可能在细胞骨架和/或细胞粘附中起作用？ 将通过以下方法检验movo基因在肌动蛋白细胞骨架重组和/或细胞粘附中携带额外功能的假设：a）检测movo过表达或缺失对小鼠角质形成细胞中细胞骨架/粘附的影响，和B）检测movo过表达或缺失对具有异常水平movo基因产物的敲除小鼠和转基因小鼠中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.