Functional analysis of zebrafish GDNF.
We have identified zebrafish orthologues of glial cell line-derived neurotrophic factor (GDNF) and the ligand-binding component of its receptor GFRalpha1. We examined the mRNA expression pattern of these genes in the developing spinal cord primary motor neurons (PMN), kidney, and enteric nervous systems (ENS) and have identified areas of correlated expression of the ligand and the receptor that suggest functional significance. Many aspects of zebrafish GDNF expression appear conserved with those reported in mouse, rat, and avian systems. In the zebrafish PMN, GFRalpha1 is only expressed in the CaP motor neuron while GDNF is expressed in the ventral somitic muscle that it innervates. To test the functional significance of this correlated expression pattern, we ectopically overexpressed GDNF in somitic muscle during the period of motor axon outgrowth and found specific perturbations in the pattern of CaP axon growth. We also depleted GDNF protein in zebrafish embryos using morpholino antisense oligos and found that GDNF protein is critical for the development of the zebrafish ENS but appears dispensable for the development of the kidney and PMN.
Shepherd
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Department of Biological Structure, University of Washington, Seattle, Washington 98195, USA.
Beattie
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Raible
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D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D002874:Chromosome Mapping; D029721:Drosophila Proteins; D017615:Enteric Nervous System / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D017403:In Situ Hybridization; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D019170:Somites / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins
D029721:Drosophila Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008024:Ligands; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D029961:Zebrafish Proteins; C495042:gdnfa protein, zebrafish; C494996:gfra1a protein, zebrafish; C494997:gfra1b protein, zebrafish; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila