During cutaneous wound healing, increased proliferation and migration of epidermal keratinocytes is essential for efficient re-epithelialization of the
wound and restoration of barrier function to the skin. Although numerous cell culture studies have identified
intracellular signaling proteins that control proliferation and migration in response to extracellular cues from the
wound microenvironment, confirming their importance in wound healing requires appropriate in vivo models. The Rho-family
guanosine triphosphatase (
GTPase) Rac1 is an effector of cellular responses to
growth factors,
cytokines, and adhesion
proteins present in
wounds, and it has long been suspected to be an important regulator of wound healing. Two different genetic models now confirm an essential role for Rac1 in wound healing and, further, identify a dual role for Rac1 in promoting keratinocyte migration and proliferation during
wound re-epithelialization. This sets the stage for determining which of the known Rac1 pathways are critical for
wound repair in vivo and for linking these pathways to specific
integrin or
growth factor receptors that mediate cellular responses to cues from the
wound environment. Together with studies that implicate Rac1 in maintaining epidermal stem cell populations, these findings lay the foundation for identifying distinct epidermal compartments from which Rac1 controls different aspects of
wound re-epithelialization.