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. In the past year, to identify EDA target genes, we have done the expression profiling to infer genes differentially expressed at various developmental time points in primary keratinocyte cultures established from wild-type and Tabby embryonic skin. By gene expression profiling, we found quite different cohort of genes that significantly affected in Tabby keratinocytes including Tbx1, Bmp7 and Jag1. Their functions under Eda regulation are now targets for further study.
| Tocchini-Valentini, Glauco P; Tocchini-Valentini, Marta A; Schlessinger, David (2009) How to build a kangaroo the way a kangaroo builds itself. FASEB J 23:3257-9 |
| Esibizione, Diana; Cui, Chang-Yi; Schlessinger, David (2008) Candidate EDA targets revealed by expression profiling of primary keratinocytes from Tabby mutant mice. Gene 427:42-6 |
