Developmentally regulated expression of Netrin-1 and -3 in the embryonic mouse molar tooth germ

The Netrins form a small, conserved family of laminin-related signaling proteins regulating axon guidance in the developing nervous system. Here, we analyzed the roles of Netrin-1 and -3 in trigeminal axon guidance to the first lower molar of the embryonic mouse. Netrin-1 showed a restricted epithelial expression domain buccal to the tooth germ, toward which the pioneer tooth axons initially appear to navigate. Later, before birth, transcripts were colocalized with nerve fibers around the bell stage tooth germ. Analysis of Netrin-1-deficient mice, however, did not reveal any obvious disturbances in the axon growth or pattern of tooth innervation. In contrast, Netrin-3 showed a prominent, distinct expression in the axon pathway and target field mesenchyme around the tooth. Hence, it is possible that Netrin-3 may regulate pioneer axon growth toward and within the embryonic tooth target field.