The semaphorins are a family of conserved proteins with variable membrane anchorage that control axon steering and branching. They are also involved in organogenesis, vascularization and tumor progression, and function in both the neural and immune systems. Semaphorin 7A (Sema7A) affects immune cell function including chemotaxis and, due to its homology to the viral SemVA and the behavior of other semaphorins in the neural system, was thought to function with the plexin-C1 receptor to regulate neuronal events. In the July 24 Nature, Jeroen Pasterkamp and colleagues at the Department of Neuroscience at the Johns Hopkins University School of Medicine show that Sema7A functions independently of plexin-C1, interacting with the β1-integrin receptor to modulate axon outgrowth via the downstream signaling targets of the integrin receptors, including focal adhesion kinase and mitogen-activated protein kinase (Nature, 424:398-425, July 24, 2003).