11.    Determining the molecular and cellular basis of hair follicle induction. 
Gavin Richardson, Durham University, Durham, UK

The mammalian epidermis and hair follicle (HF) are unique developmental systems characterized by their capacity for continuous renewal (epidermis) and cycling (HF). The HF arises due to a series of reciprocal signaling interactions between the embryonic skin epithelium and mesenchyme. These early events of HF induction take place at around 14.5 days post coitus (dpc) in the mouse, concomitant with the transformation of the simple epithelium to a more differentiated and stratified epithelium. In this study, we performed microarray analysis to study global gene expression changes during epidermal morphogenesis in the mouse at 12 hour intervals between 12.5 and 15.5 dpc. At each time point, we used enzymatic and mechanical techniques to separate the embryonic skin dermis from the epidermis and each RNA sample was hybridized to Affymetrix MOE430A arrays. Our list of significant transcriptional changes has uncovered several potential new players in dermal and HF morphogenesis in addition to corroborating previously identified signaling pathways (Wnt, BMP, Shh, FGF, and EGF). Differential expression throughout the various time points was validated by RT-PCR and expression of selected genes examined at the RNA and protein level by in situ hybridization and immunohistochemistry, respectively. We have been using an embryonic skin organ culture model, to investigate the effects of specific genes on normal hair follicle morphogenesis. The EGFR mediated signaling pathway has previously been demonstrated to be important in HF morphogenesis. Having found differential expression of members of the EGF family we investigated the role of these, and two other genes (Chordin Like 1 and Gremlin both having known roles in BMP signaling) by means of embryonic skin organ culture, to determine their effect on normal hair follicle morphogenesis.