O2 sensing: only skin deep?

The transcription factor HIF-1 mediates adaptive responses to hypoxia, and its activity is negatively regulated by O2-dependent binding of the von Hippel-Lindau (VHL) protein. In this issue, Boutin et al. (2008) use conditional knockout mice to demonstrate that sensing of O2 by keratinocytes in the epidermis leads to alterations in cutaneous blood flow that affect the production of the hormone erythropoietin, thereby modulating red blood cell production and the O2-carrying capacity of blood.