Glial cell line-derived neurotrophic factor defines the path of developing and regenerating axons in the lateral line system of zebrafish.

How the peripheral axons of sensory neurons are guided to distant target organs is not well understood. Here we examine this question in the case of the posterior lateral line (PLL) system of zebrafish, where sensory organs are deposited by a migrating primordium. Sensory neurites accompany this primordium during its migration and are thereby guided to their prospective target organs. We show that the inactivation of glial cell line-derived neurotrophic factor (GDNF) signaling leads to defects of innervation and that these defects are due to the inability of sensory axons to track the migrating primordium. GDNF signaling is also used as a guidance cue during axonal regeneration following nerve cut. We conclude that GDNF is a major determinant of directed neuritic growth and of target finding in this system, and we propose that GDNF acts by promoting local neurite outgrowth.