Developmental Genes in Sebaceous Glands and Keratinocytes

皮脂腺和角质形成细胞中的发育基因

• 批准号: 7732282
• 负责人: David Schlessinger
• 金额: $ 33.02万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7732282
• 关键词: Acne; Development; Developmental Gene; Gene Expression; Genes; Goals; Growth; Growth and Development function; Hair follicle structure; Human; Maintenance; Mus; Pathway interactions; Process; Sebaceous Glands; Signal Pathway; Skin; Sweat Glands; appendage; keratinocyte; response; size; skin disorder

In extensive studies, we found that the Eda gene (ZO1 AG000643-10 LG) is deeply involved in the initiation and specification of several skin appendages, including hair follicles and sweat glands -- both in humans and in mice defective in the cognate Eda gene. However, we found that sebaceous glands develop as a further appendage on hair follicles, form independently of the Eda pathway; but they become larger in response to Eda action. This has led us to investigate broader aspects of skin appendage formation in two ways. To understand better the the repertoire of gene involved in the overall process of skin appendage formation, we have isolated keratinocytes from both Eda-positive and Eda-ablated mice, and are carrying out gene expression analyses to assess active signaling pathways that are dependent or independent of Eda action. A subset of those genes are expected to act in sebaceous gland formation; and in parallel, we focus on "trophic" (growth) effects of Eda in sebaceous glands by 1) examining in detail the genes expressed specifically during sebaceous gland formation and in the sebocytes that populate them; and 2) determining the effects of graded levels of Eda on the processes of growth and development.

在广泛的研究中，我们发现EDA基因（ZO1 AG000643-10 LG）深深地参与了几种皮肤附属物的启动和规范，包括毛囊和汗腺，无论是在人类和小鼠中，在Cognate EDA基因中有缺陷。 但是，我们发现皮脂腺作为毛囊上的进一步附属物发展，独立于EDA途径。但是，它们对EDA行动的响应变得更大。 这使我们通过两种方式研究了皮肤附属形成的更广泛方面。为了更好地了解与皮肤附属形成整体过程有关的基因曲目，我们已经从EDA阳性和EDA启动的小鼠中分离出了角质形成细胞，并且正在进行基因表达分析，以评估依赖或独立于EDA动作的活动信号传导途径。这些基因的一部分有望在皮脂腺形成中起作用。同时，我们将重点放在皮脂腺中EDA在皮脂腺中的“营养”（生长）效应1）详细检查在皮脂腺形成期间专门表达的基因以及在填充它们的皮脂细胞中； 2）确定EDA水平水平对生长和发展过程的影响。

项目成果

Analysis of the temporal requirement for eda in hair and sweat gland development.

• DOI: 10.1038/jid.2008.318
• 发表时间: 2009-04
• 期刊: The Journal of investigative dermatology