In the mouse olfactory system, much of neural map formation takes place autonomously by axon-axon interactions of primary neurons without involving target cues. However, proper connections to the second-order neurons are needed to convert sensory stimuli correctly to higher cortical neurons in the OC. What mediates the synapse formation between axons of olfactory sensory neurons (OSNs) and dendrites of mitral/tufted (M/T) cells? Here we report that a pair of signaling molecules, Semaphorin 7A (Sema7A) expressed by OSNs and its receptor Plexin C1 (PlxnC1) expressed by M/T cells, are essential for triggering activity-dependent synapse formation in the mouse olfactory bulb (OB). In both knockout (KO) mice for either Sema7A or PlxnC1, synapse formation and dendrite maturation are perturbed. The same phenotype is also observed in the KO of cyclic nucleotide gated (CNG) channels, as Sema7A expression in OSNs is regulated in an activity-dependent manner. Surprisingly, this phenotype of dendrite maturation in the CNG KO is rescued by the forced expression of Sema7A alone with the OR gene promoter. We can therefore conclude that Sema7A-PlxnCl signaling plays a key role in triggering the synapse formation of M/T cells in the OB.