Described as secreted and membrane-bound proteins important for neural pathfinding, the class of proteins called Semaphorins are expressed in multiple tissue types and are involved in diverse biologic processes. In this study, we describe the function of Semaphorin 7a, a membrane-bound Semaphorin known to stimulate neurite outgrowth, on human melanocytes. We show that Semaphorin 7a is expressed by human keratinocytes and fibroblasts in vitro and in vivo and that melanocytes express Plexin C1, a receptor for Semaphorin 7a. Upregulation of Semaphorin 7a was observed in fibroblasts treated with UV irradiation, a potent stimulus for melanocyte dendricity. Because of the importance of melanocyte dendrites in cutaneous photoprotection, we performed functional studies examining the effect of Semaphorin 7a in melanocyte dendrite formation. We also examined the contribution of beta1-integrin and Plexin C1 receptor signaling in mediating effects of Semaphorin 7a in melanocytes. We show that Semaphorin 7a induces significant melanocyte spreading and dendricity in human melanocytes. Furthermore, we show that beta1-integrins and Plexin C1 receptors are ligands for Semaphorin 7a, and that signaling by these receptors has opposing effects on Semaphorin 7a-induced dendrite formation.