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First published online 3 December 2003
doi: 10.1242/dev.00912

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Roles for GFR1 receptors in zebrafish enteric nervous system development

Iain T. Shepherd^1,2,, Jacy Pietsch², Stone Elworthy^3,*, Robert N. Kelsh³ and David W. Raible¹

¹ Department of Biological Structure, University of Washington, Box 357420, Seattle, WA 98195, USA
² Department of Biology, Emory University, Rollins Research Center, 1510 Clifton Road, Atlanta GA 30322, USA
³ Centre for Regenerative Medicine and Developmental Biology Program, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK

Author for correspondence (e-mail: ishephe{at}emory.edu)

Accepted 8 October 2003

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 GFR1 and GFR2 are functionally equivalent.

Key words: Zebrafish, GFR1, GFR2, Ret, GDNF, Enteric nervous system, Morpholino oligonucleotides

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