Growth cone extension is guided by extracellular factors during the brain development but the underlying cellular mechanisms remain largely unclear. Here, we examined the potential function of class-3 semaphorins in cultured cerebellar granule cells. We found neuropilin-2 (NP2), the high-affinity receptor for semaphorin-3F (Sema3F), is highly expressed in cerebellar granule cells. An extracellular gradient of Sema3F-triggered an NP2-dependent attractive turning of the growth cone of cultured cerebellar granule cells. This Sema3F-triggered growth cone attraction was abolished by inhibition of the cGMP signaling pathway and reduced by elevating the intracellular cGMP level. Furthermore, Sema3F partially rescued the collapse induced by inhibition of basal cGMP in granule cells. Thus, Sema3F may act as a chemoattractant for the growth cone of cerebellar granule cells through cGMP signaling pathway. (c) 2007 Elsevier Inc. All rights reserved.