Neural crest cells (NCCs) are migratory cells that differentiate into several cell types, including neurons and bone cells. NCCs proliferate before and throughout their migration and differentiation. Wnt/TCF signalling helps to control this proliferation but are any other factors involved? Berndt and Halloran now report that the guidance molecule semaphorin 3d (Sema3d) acts downstream of Wnt/TCF signalling to promote NCC proliferation and development in the zebrafish hindbrain (see p. 3983). The researchers show that morpholino-mediated knockdown of Sema3d inhibits the proliferation of hindbrain neuroepithelial cells at the time of their epithelial-mesenchymal transition into migratory NCCs. It also reduces the number of migratory NCCs and disrupts the development of NCC derivatives. Other results indicate that Sema3d lies downstream of Wnt/TCF signalling; for example, Sema3d overexpression rescues the reduced NCC proliferation caused by expression of a dominant-repressor form of TCF. The researchers conclude from their experiments that Sema3d function is important for regulating the cell cycle of NCCs and for their subsequent development.