Roles for GFRalpha1 receptors in zebrafish enteric nervous system development.
Components of the zebrafish GDNF receptor complex are expressed very early in the development of enteric nervous system precursors, and are already present as these cells begin to enter the gut and migrate caudally along its length. Both gfra1a and gfra1b as well as ret are expressed at this time, while gfra2 expression, the receptor component that binds the GDNF-related ligand neurturin, is not detected until the precursors have migrated along the gut. Gfra genes are also expressed in regions of the zebrafish brain and peripheral ganglia, expression domains conserved with other species. Enteric neurons are eliminated after injection with antisense morpholino oligonucleotides against ret or against both Gfra1 orthologs, but are not affected by antisense oligonucleotides against gfra2. Blocking GDNF signaling prevents migration of enteric neuron precursors, which remain positioned at the anterior end of the gut. Phenotypes induced by injection of antisense morpholinos against both Gfra orthologs can be rescued by introduction of mRNA for gfra1a or for gfra2, suggesting that GFRalpha1 and GFRalpha2 are functionally equivalent.
Shepherd
Iain T
IT
Department of Biological Structure, University of Washington, Box 357420, Seattle, WA 98195, USA. ishephe@empory.edu
Pietsch
Jacy
J
Elworthy
Stone
S
Kelsh
Robert N
RN
Raible
David W
DW
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D017124:Conserved Sequence; D004625:Embryo, Nonmammalian / Q000502:physiology; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins
C494987:GFRA1 protein, human; C494990:GFRA2 protein, human; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D011518:Proto-Oncogene Proteins; D029961:Zebrafish Proteins; C494996:gfra1a protein, zebrafish; C494997:gfra1b protein, zebrafish; C494998:gfra2a protein, zebrafish; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C546313:Ret protein, zebrafish