GFRα3 is a component of the receptor for the neurotrophic factor artemin. The role of GFRα3 in nervous system development was examined by generating mice in which the Gfrα3 gene was disrupted. The Gfrα3-/-) 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, Gfrα3 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 GFRα3-mediated signaling is required both for the rostral migration of SCG precursors and for the survival of mature SCG neurons.
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