Illustration depicting the molecular pathways involved in mast cell recruitment to neurofibromas. A neurofibromin-deficient Schwann cell (Nf1^–/–) secretes five times the normal Kit ligand, which serves as a chemoattractant for mast cells expressing c-Kit. Mast cell migration is mediated by the Ras/PI3K/Rac2 signal transduction pathway, which is enhanced in Nf1^+/– cells. Although not shown, endothelial cells also play a role in mast cell migration through the interaction of the endothelial cell VCAM-1 receptor and α4β1 integrin of the mast cell. Heterozygous inactivation of Nf1 promotes rapid mast cell haptotaxis specifically on α4β1 integrins in response to KitL. It is known that mast cells are activated in neurofibromas and degranulate; however it is yet to be determined if and how the presence of mast cells induces tumor progression. Figure courtesy of D. Wade Clapp, Indiana University School of Medicine. KitL, Kit ligand.