Regulation of Epidermal Development and Differention

Rockefeller University, New York NY

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): [unreadable] Our global objective is to elucidate the mechanisms underlying differentiation and development in mammalian epidermis and hair. To achieve this goal, we focus on the regulatory controls that govern [unreadable] expression of keratins, the major structural proteins of these cells. Understanding how this complex [unreadable] pattern of keratin gene expression is established is key to elucidating how these cells develop and [unreadable] how these processes go awry in human skin disorders. Elucidating how K5 and K14 promoter activity [unreadable] is controlled is prerequisite to developing cultured keratinocytes as therapeutic agents for drug [unreadable] delivery and gene therapy, an extension of their current use in burn operations. Our studies have [unreadable] already unveiled some transcription factors, including the AP2 family, in regulating K5 and K14 gene [unreadable] expression, and the Tcf/Lef family of transcription factors in regulating the hair keratin genes. Given [unreadable] the multiplicity of factors involved in regulating transcription in the skin, a complementary microarray [unreadable] approach is needed to provide a database of the global changes in transcription factor gene [unreadable] expression during skin development. Preliminary analyses have already illuminated which of the AP2 [unreadable] family members and enhancer factor associates are likely to be key in governing transcription during [unreadable] keratinocyte specification. Additionally, a database of developmental patterns of gene expression will [unreadable] greatly facilitate our interpretation of AR31737-approved arrays of skin-specific transcription factor [unreadable] knockout mice, and enhance the identification of downstream target genes. The database will serve [unreadable] as the foundation for integrating and achieving our funded goals of AR31737 research aimed at [unreadable] elucidating the regulatory mechanisms that govern epidermal and hair follicle gene expression. The [unreadable] database will be an excellent resource for future dissection of the downstream pathways involved, [unreadable] and for expediting our progress in understanding how cell fate decisions are made in normal and [unreadable] disease states. [unreadable] [unreadable] [unreadable]