Abstract
GFR alpha3 is a component of the receptor for the neurotrophic factor artemin. The role of GFR alpha3 in nervous system development was examined by generating mice in which the Gfr alpha3 gene was disrupted. The Gfr alpha3-/- 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 alpha3 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 alpha3-mediated signaling is required both for the rostral migration of SCG precursors and for the survival of mature SCG neurons.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Death / physiology
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Cell Movement / genetics
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Cell Movement / physiology*
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Cell Survival / physiology
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Drosophila Proteins*
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Genotype
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Immunohistochemistry
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In Situ Hybridization
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Mice
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Mice, Knockout
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Nerve Growth Factors / metabolism*
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Nerve Tissue Proteins / metabolism*
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Neurons / physiology*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / physiology*
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Receptors, Nerve Growth Factor / genetics*
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Receptors, Nerve Growth Factor / metabolism*
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Superior Cervical Ganglion / cytology
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Superior Cervical Ganglion / embryology*
Substances
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Artn protein, mouse
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Drosophila Proteins
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Nerve Growth Factors
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Nerve Tissue Proteins
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Proto-Oncogene Proteins
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Receptors, Nerve Growth Factor
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases
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Ret protein, Drosophila