Genetic Control of Epidermal Appendage Development

表皮附属物发育的遗传控制

• 批准号: 6512229
• 负责人: CYNTHIA A LOOMIS
• 金额: $ 24.65万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-16 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6512229
• 关键词: cell differentiation; developmental genetics; genetically modified animals; histogenesis; laboratory mouse; mutant; skin; skin derivative; sweat glands

DESCRIPTION: (Verbatim) Each year 1/2,000 infants is born with a serious skin or skin appendage defect and many more are diagnosed with skin anomalies in the first six months of life. Many of these defects result from mutations in genes required for regulating the carefully choreographed, bi-directional signaling cascades between embryonic dermis and epidermis that is necessary for normal skin development. Our data indicate that complex interactions between the regulatory genes Engrailed- (En 1), Wnt7a and Lmxlb are critical for normal nail and eccrine gland development. More specifically, Eni appears to function at three stages of appendage development: patterning, morphogenesis and differentiation. We propose to: 1. To provide a foundation for our mutant studies by delineating the normal steps of eccrine gland and nail morphogenesis and cytodifferentiation using both morphological and molecular criteria. 2. To determine the requirements for En 1, Wnt7a and Lmx lb in eccrine gland and nail development by characterizing the alterations in morphology and marker gene expression patterns that occur in single and double loss-of-function mutants. 3. To determine at what stages in development En1 is required to promote eccrine gland formation and inhibit ectopic nail-like differentiation by abrogating En I gene function at different developmental stages using a conditional En 1 mutant allele. 4. To determine whether ectodermally expressed En1 is sufficient to direct eccrine gland development and to inhibit nail/hair development by ectopically expressing En 1 using retroviral vectors.

描述：（逐字逐句）每年有1/2,000的婴儿出生时患有严重的皮肤病 或皮肤附件缺陷，更多的人被诊断为皮肤异常， 生命的前六个月。这些缺陷中有许多是由基因突变引起的 调节精心设计的双向信号 胚胎真皮和表皮之间的级联，这是必要的正常 皮肤发育我们的数据表明， 调节基因Engrailed-（En 1）、Wnt 7a和Lmxlb对于正常的 指甲和外分泌腺发育。更具体地说，埃尼似乎在发挥作用， 在附肢发育的三个阶段：模式化，形态发生和 分化我们建议： 1.为我们的突变研究提供基础， 小汗腺和指甲形态发生和细胞分化的步骤， 形态学和分子学标准。 2.确定外分泌腺对En 1、Wnt 7a和Lmx 1b的需要量 通过表征形态学和标记物的改变来观察 基因表达模式，发生在单和双功能丧失 变种人 3.确定在开发的哪个阶段需要促进En 1 外泌腺形成和抑制异位指甲样分化 使用酶在不同发育阶段废除En I基因功能 条件性En 1突变等位基因。 4.为了确定外胚层表达的En 1是否足以指导 外分泌腺发育和通过异位抑制指甲/毛发发育 使用逆转录病毒载体表达En 1。