745 Regional expression of secreted WNT inhibitors dictates formation of hairless and poorly haired skin

Different regions of mammalian skin vary in characteristics such as thickness, and hair follicle sweat gland presence, size density, that are reflected differential responses to injury disease. Positional information resides the upper dermis but responsible molecular mechanisms poorly understood. To uncover these, we carried out comparative scRNA-seq mouse embryonic dorsal, ear plantar skin. This revealed regional expression several secreted Wnt inhibitors, including Dkk2 Sostdc1, suggesting modulation signaling an important mechanism controlling heterogeneity. In line with this, showed previously Dkk2-null mice develop regenerative follicles normally hairless However, other had normal density size. Loss Sostdc1 is known cause ectopic formation nipple skin, extra vibrissae, larger placodes trunk We hypothesized function partially redundantly control additional features. test generated lacking both inhibitors. Double mutants displayed elevated increased compared single mutants, growth abnormally dense, long, thick on external ears. Thus, controls versus hairy haired These data support a new paradigm which, rather than being dictated by activating dermal signal postulated classical models, default pathway actively suppressed inhibitors lack or haired.