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Identification of dermal papilla-specific genes and their possible roles in hair regulation

Posted on:2003-09-10Degree:Ph.DType:Dissertation
University:New York UniversityCandidate:Cao, QiongFull Text:PDF
GTID:1464390011978293Subject:Biology
Abstract/Summary:
The hair follicle is a dynamic structure undergoing cyclic growth. Although several growth factors, hormones, and some other genes have been implicated in controlling hair growth, our knowledge of the molecules that are involved in this process is far from being completed and the underlying mechanisms are unclear. Therefore, my main goal is to identify a panel of genes that may be involved in controlling hair growth. Since dermal papilla, the mesenchymal cells of the hair follicle, but not regular skin fibroblasts, can support hair growth, we searched for molecules that are expressed preferentially in cultured dermal papilla cells vs. fibroblasts using three approaches. First, using degenerate PCR followed by differential display and random cloning, we found that several tyrosine kinases, including c-met, cdc2, and tec, were preferentially expressed in dermal papilla cells, whereas α-PDGF receptor was preferentially expressed in fibroblasts. These results were confirmed by semiquantitative PCR and the different responses of the two cell types to HGF, and PDGF-AA and PDGF-BB. Second, using DNA microarray technique, we compared the expression patterns of 6800 genes in cultured human dermal papilla cells vs. fibroblast and found that 53 genes, including p27, osteopontin, were expressed at higher levels in dermal papilla. Third, to discover novel dermal papilla-specific genes, we constructed a dermal papilla-specific subtraction library. Nine EST sequences and 25 known genes were identified from this subtraction library. The most abundant EST clone, which we named DP-1, was highly expressed in cultured dermal papilla cells, but not in culture fibroblasts or in most other rat tissues examined (except at very low levels in stomach and ovary). The full-length DP-1 cDNA is 2,283 bp, encoding a DP-1 protein of 502 amino acids. DP-1 was a glycoprotein with a signal peptide, and its N- and C-terminal peptide sequences were homologous to collagen and olfactomedin, respectively. The DP-1 gene was localized on human chromosome 15g15-q21 and mouse chromosome 9 B-C region. Further experiments need to be performed to examine the in vivo expression patterns of these dermal papilla-specific genes and to study their roles in hair growth regulation.
Keywords/Search Tags:Genes, Hair, Dermal papilla, Growth, DP-1
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