Researchers have identified the signals and exact timing during embryonic development that dictate the fate of skin cells to be sweaty or hairy. Unlike other mammals that must pant or seek shade when overheated, humans are able to self-cool by sweating. This rather unique ability is what allows humans tolerate extreme temperatures and run marathons, for example. But the underlying mechanisms that differentiate "sweaty" or "hairy" cells remain largely unknown. To gain insights, Catherine Lu et al. exploited the fact that mice have skin cells that only support hair follicle (HF) generation on their dorsal back, whereas the skin cells on their feet only support the generation of sweat glands (SwG). Based on differences in RNA expression between these two cell subtypes, the team found that mesenchymal-derived bone morphogenetic proteins (BMPs) were significantly enriched in the foot skin cells, compared to the hairy cells found on the backs of mice. In particular, Bmp5 was found to play a role in differentiating skin cell fates. For example, blocking Bmp5 reduced the number of sweat glands that developed in the foot skin of mice. Lu et al. identified a number of additional mechanisms behind this differentiation, such as Wnt and FGF proteins. In samples of human scalp skin, they found increased expression of BMP and FGF genes at week 17 compared to week 15, which is coincident with the shift from hair to sweat-bud formation in humans. These findings pave the way for future skin regeneration therapies, the authors say. Yung Chi Lai and Cheng-Ming Chuong discuss the advancement in a related Perspective.