GFR alpha 3, a Component of the Artemin Receptor, Is Required for Migration and Survival of the Superior Cervical Ganglion

GFR alpha 3 is a component of the receptor for the neurotrophic factor artemin. The role of GFR alpha 3 in nervous system development was examined by generating mice in which the Gfr alpha 3 gene was disrupted. The Gfr alpha 3 super(-/-) mice exhibited severe defects in the superior cervical ganglion (SCG), whereas other ganglia appeared normal. SCG precursor cells in the mutant embryos failed to migrate to the correct position, and they subsequently failed to innervate the target organs. In wild-type embryos, Gfr alpha 3 was expressed in migrating SCG precursors, and artemin was expressed in and near the SCG. After birth, SCG neurons in the mutant mice underwent progressive cell death. These observations suggest that GFR alpha 3-mediated signaling is required both for the rostral migration of SCG precursors and for the survival of mature SCG neurons.