Fig. 6.

Hypothetical model for mechanisms underlying pre-placode stage neural crest-derived epidermal Wnt signalling. a Neural crest cells that have invaded the ectoderm [34] are in close apposition with epidermal stem cells at pre-placode stages. Neural crest cells express Wnt proteins [8, 44] and their cognate receptors [43, 46, 47, 49]. Therefore neural crest cells can undergo autocrine Wnt signalling. Epidermal stem cells within the future placode express the Eda-A1 receptor, Edar [3, 32]. No activated beta-catenin indicative of Wnt signalling in the dermis is detected at that early stage of hair development [3]. b As a consequence of cell-autonomous Wnt signalling, neural crest cells produce Wnt target genes, including Eda-A1 ([21]; this study). c Eda-A1/Edar signalling in epidermal cells leads to DKK4 expression. In Wnt1-cre(+/−)::Pygo(−/−) mice, it is expected that the DKK:Wnt ratio is altered and Eda-A1 protein levels are reduced. Together these changes can explain the here observed disturbances in hair follicle thickness, hair density, as well as zig-zag hair formation and morphology