Developmental Genes in Sebaceous Glands and Keratinocytes

在广泛的研究中，我们发现Eda基因（ZO1 AG000643-10 LG）在人类和同源Eda基因缺陷的小鼠中深入参与了包括毛囊和汗腺在内的几种皮肤附属物的启动和指定。然而，我们发现皮脂腺作为毛囊的进一步附属物发展，独立于Eda途径形成；但它们会在Eda的作用下变大。这导致我们以两种方式研究皮肤附属物形成的更广泛方面。为了更好地了解参与整个皮肤附件形成过程的基因库，我们从Eda阳性和Eda消融的小鼠中分离了角质形成细胞，并进行了基因表达分析，以评估依赖或独立于Eda作用的活跃信号通路。这些基因的一个子集预计在皮脂腺形成中起作用；同时，我们关注Eda在皮脂腺中的“营养”（生长）效应：1)详细检查皮脂腺形成过程中特异性表达的基因和填充皮脂腺的皮脂细胞；2)确定Eda分级水平对生长发育过程的影响。

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.