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（ZO 1 AG 000643 -10 LG）与几种皮肤附属物的启动和规范密切相关，包括毛囊和汗腺-无论是在人类还是在同源Eda基因缺陷的小鼠中。 然而，我们发现皮脂腺作为毛囊上的进一步附属物而发育，其形成独立于EDA途径;但它们响应于EDA作用而变大。 这使我们从两个方面研究了皮肤附件形成的更广泛的方面。为了更好地了解参与皮肤附件形成的整个过程的基因库，我们从Eda阳性和Eda消融小鼠中分离出角质形成细胞，并进行基因表达分析以评估依赖或独立于Eda作用的活性信号传导途径。这些基因的一个子集预计将在皮脂腺形成中发挥作用;同时，我们通过以下方式关注Eda在皮脂腺中的“营养”（生长）作用：1）详细检查皮脂腺形成期间和填充它们的皮脂细胞中特异性表达的基因; 2）确定Eda的分级水平对生长和发育过程的影响。

项目成果

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

分析头发和汗腺发育中EDA的时间需求。

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