Gene Symbol: ret
Description: ret proto-oncogene receptor tyrosine kinase
Alias: c-ret, cret, etID315074.13, ret1, wu:fd13h01, proto-oncogene tyrosine-protein kinase receptor Ret, receptor tyrosine kinase
Species: zebrafish

Top Publications

  1. Nichane M, Van Campenhout C, Pendeville H, Voz M, Bellefroid E. The Na+/PO4 cotransporter SLC20A1 gene labels distinct restricted subdomains of the developing pronephros in Xenopus and zebrafish embryos. Gene Expr Patterns. 2006;6:667-72 pubmed
    ..Together, our data reveal that the zebrafish and Xenopus pronephros have non-identical proximo-distal organizations. ..
  2. Majumdar A, Lun K, Brand M, Drummond I. Zebrafish no isthmus reveals a role for pax2.1 in tubule differentiation and patterning events in the pronephric primordia. Development. 2000;127:2089-98 pubmed
  3. Fisher S, Grice E, Vinton R, Bessling S, McCallion A. Conservation of RET regulatory function from human to zebrafish without sequence similarity. Science. 2006;312:276-9 pubmed
    ..We have used a transposon-based transgenic assay in zebrafish to evaluate noncoding sequences at the zebrafish ret locus, conserved among teleosts, and at the human RET locus, conserved among mammals...
  4. Postlethwait J, Yan Y, Gates M, Horne S, Amores A, Brownlie A, et al. Vertebrate genome evolution and the zebrafish gene map. Nat Genet. 1998;18:345-9 pubmed
    ..This zebrafish gene map will facilitate molecular identification of mutated zebrafish genes, which can suggest functions for human genes known only by sequence. ..
  5. Gau P, Curtright A, Condon L, Raible D, Dhaka A. An ancient neurotrophin receptor code; a single Runx/Cbf? complex determines somatosensory neuron fate specification in zebrafish. PLoS Genet. 2017;13:e1006884 pubmed publisher
  6. Field H, Kelley K, Martell L, Goldstein A, Serluca F. Analysis of gastrointestinal physiology using a novel intestinal transit assay in zebrafish. Neurogastroenterol Motil. 2009;21:304-12 pubmed publisher
    ..This may facilitate the use of the zebrafish for investigating the effect of compounds and candidate genes on gastrointestinal motility. ..
  7. Bonora E, Bianco F, Cordeddu L, Bamshad M, Francescatto L, Dowless D, et al. Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction. Gastroenterology. 2015;148:771-782.e11 pubmed publisher
    ..This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis...
  8. Rothschild S, Francescatto L, Drummond I, Tombes R. CaMK-II is a PKD2 target that promotes pronephric kidney development and stabilizes cilia. Development. 2011;138:3387-97 pubmed publisher
    ..We conclude that CaMK-II is a crucial effector of PKD2 Ca²? that both promotes morphogenesis of the pronephric kidney and stabilizes primary cloacal cilia. ..
  9. Schuster K, Dambly Chaudiere C, Ghysen A. Glial cell line-derived neurotrophic factor defines the path of developing and regenerating axons in the lateral line system of zebrafish. Proc Natl Acad Sci U S A. 2010;107:19531-6 pubmed publisher
    ..We conclude that GDNF is a major determinant of directed neuritic growth and of target finding in this system, and we propose that GDNF acts by promoting local neurite outgrowth. ..

More Information


  1. Reichenbach B, Delalande J, Kolmogorova E, Prier A, Nguyen T, Smith C, et al. Endoderm-derived Sonic hedgehog and mesoderm Hand2 expression are required for enteric nervous system development in zebrafish. Dev Biol. 2008;318:52-64 pubmed publisher
    ..Furthermore we show that endoderm and HH signaling, but not hand2, regulate gdnf expression in the intestine, highlighting a central role of endoderm and SHH in patterning the intestine and the ENS. ..
  2. Van Campenhout C, Nichane M, Antoniou A, Pendeville H, Bronchain O, Marine J, et al. Evi1 is specifically expressed in the distal tubule and duct of the Xenopus pronephros and plays a role in its formation. Dev Biol. 2006;294:203-19 pubmed
    ..Together, these data indicate that Evi1 plays a role in the proximo-distal patterning of the pronephros and suggest that it may do so by functioning as a CtBP dependent repressor. ..
  3. López Rivera E, Liu Y, Verbitsky M, Anderson B, Capone V, Otto E, et al. Genetic Drivers of Kidney Defects in the DiGeorge Syndrome. N Engl J Med. 2017;376:742-754 pubmed publisher
    ..Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.). ..
  4. Jurynec M, Xia R, Mackrill J, Gunther D, Crawford T, Flanigan K, et al. Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle. Proc Natl Acad Sci U S A. 2008;105:12485-90 pubmed publisher
  5. Marcos Gutierrez C, Wilson S, Holder N, Pachnis V. The zebrafish homologue of the ret receptor and its pattern of expression during embryogenesis. Oncogene. 1997;14:879-89 pubmed
    The c-ret proto-oncogene, a member of the receptor tyrosine kinase gene superfamily, plays a critical role in the development of the excretory system and the enteric and autonomic nervous systems of mammalian embryos...
  6. Heanue T, Boesmans W, Bell D, Kawakami K, Vanden Berghe P, Pachnis V. A Novel Zebrafish ret Heterozygous Model of Hirschsprung Disease Identifies a Functional Role for mapk10 as a Modifier of Enteric Nervous System Phenotype Severity. PLoS Genet. 2016;12:e1006439 pubmed publisher
    ..We show that ret mutant zebrafish exhibit cellular, physiological and genetic features of HSCR, including absence of intestinal ..
  7. Saarenpää T, Kogan K, Sidorova Y, Mahato A, Tascón I, Kaljunen H, et al. Zebrafish GDNF and its co-receptor GFR?1 activate the human RET receptor and promote the survival of dopaminergic neurons in vitro. PLoS ONE. 2017;12:e0176166 pubmed publisher
    ..factor (GDNF) is a ligand that activates, through co-receptor GDNF family receptor alpha-1 (GFR?1) and receptor tyrosine kinase "RET", several signaling pathways crucial in the development and sustainment of multiple neuronal ..
  8. Kashuk C, Stone E, Grice E, Portnoy M, Green E, Sidow A, et al. Phenotype-genotype correlation in Hirschsprung disease is illuminated by comparative analysis of the RET protein sequence. Proc Natl Acad Sci U S A. 2005;102:8949-54 pubmed
    ..In this study, the RET receptor tyrosine kinase serves as a model disease gene in which a broad spectrum (> or = 116) of disease-associated mutations ..
  9. Stewart R, Arduini B, Berghmans S, George R, Kanki J, Henion P, et al. Zebrafish foxd3 is selectively required for neural crest specification, migration and survival. Dev Biol. 2006;292:174-88 pubmed
  10. Wang S, Xu P, Thorsen J, Zhu B, de Jong P, Waldbieser G, et al. Characterization of a BAC library from channel catfish Ictalurus punctatus: indications of high levels of chromosomal reshuffling among teleost genomes. Mar Biotechnol (NY). 2007;9:701-11 pubmed
    ..This indicates that comparative genome analysis may provide shortcuts to genome analysis in catfish, especially for short genomic regions once the conserved syntenies are identified. ..
  11. Mudumana S, Hentschel D, Liu Y, Vasilyev A, Drummond I. odd skipped related1 reveals a novel role for endoderm in regulating kidney versus vascular cell fate. Development. 2008;135:3355-67 pubmed publisher
  12. Facello B, Castaldo L, De Martino L, Lucini C. Glial cell line-derived neurotrophic factor in Purkinje cells of adult zebrafish: an autocrine mode of action?. Neurosci Lett. 2009;465:133-7 pubmed publisher
    ..Its signalling is mediated by a receptorial complex GFRalpha1/RET. In the brain of adult zebrafish (Danio rerio) we previously investigated GDNF expression and localization, but no ..
  13. Shepherd I, Pietsch J, Elworthy S, Kelsh R, Raible D. Roles for GFRalpha1 receptors in zebrafish enteric nervous system development. Development. 2004;131:241-9 pubmed
    ..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 ..
  14. Parichy D, Mellgren E, Rawls J, Lopes S, Kelsh R, Johnson S. Mutational analysis of endothelin receptor b1 (rose) during neural crest and pigment pattern development in the zebrafish Danio rerio. Dev Biol. 2000;227:294-306 pubmed
    ..rerio. ..
  15. Knight R, Mebus K, D Angelo A, Yokoya K, Heanue T, Roehl H. Ret signalling integrates a craniofacial muscle module during development. Development. 2011;138:2015-24 pubmed publisher
    ..we show that the development of a subset of functionally related head muscles in the zebrafish is regulated by Ret tyrosine kinase signalling...
  16. Jiang Q, Arnold S, Heanue T, Kilambi K, Doan B, Kapoor A, et al. Functional loss of semaphorin 3C and/or semaphorin 3D and their epistatic interaction with ret are critical to Hirschsprung disease liability. Am J Hum Genet. 2015;96:581-96 pubmed publisher
    ..non-coding variants in 13 genes are known to underlie HSCR risk, with the most frequent variants in the ret proto-oncogene (RET)...
  17. Lister J, Cooper C, Nguyen K, Modrell M, Grant K, Raible D. Zebrafish Foxd3 is required for development of a subset of neural crest derivatives. Dev Biol. 2006;290:92-104 pubmed
  18. Cretekos C, Grunwald D. alyron, an insertional mutation affecting early neural crest development in zebrafish. Dev Biol. 1999;210:322-38 pubmed
  19. Cheng W, Tang C, Gui H, So M, Lui V, Tam P, et al. Depletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype. World J Gastroenterol. 2015;21:2040-6 pubmed publisher
    ..We also studied the expressions of ret and phox2bb, which are involved in ENS development, in the ikbkap morpholino injected embryos by quantitative ..
  20. Montero Balaguer M, Lang M, Sachdev S, Knappmeyer C, Stewart R, De La Guardia A, et al. The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish. Dev Dyn. 2006;235:3199-212 pubmed
    ..Further analysis of mosm188 mutants and foxd3 morphants revealed that NC cells are initially formed, suggesting that foxd3 function is required to maintain the pool of NC progenitors. ..
  21. Coelho M, Tannuri U, Benditt I, Santos M. Studies of RET gene expression and acetylcholinesterase activity in a series of sporadic Hirschsprung's disease. Pediatr Surg Int. 2008;24:1017-21 pubmed publisher
    The purpose is to present the studies of RET gene expression and acetylcholinesterase activity in 23 patients operated for Hirschsprung's disease (HD)...
  22. Taylor C, Montagne W, Eisen J, Ganz J. Molecular fingerprinting delineates progenitor populations in the developing zebrafish enteric nervous system. Dev Dyn. 2016;245:1081-1096 pubmed publisher
    ..subpopulations based on coexpression of three genes essential for normal ENS development: phox2bb, sox10, and ret. Our data suggest that combinatorial expression of these genes delineates three major ENS progenitor subpopulations,..
  23. Emison E, McCallion A, Kashuk C, Bush R, Grice E, Lin S, et al. A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature. 2005;434:857-63 pubmed
    ..a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes...
  24. Rastegar S, Hess I, Dickmeis T, Nicod J, Ertzer R, Hadzhiev Y, et al. The words of the regulatory code are arranged in a variable manner in highly conserved enhancers. Dev Biol. 2008;318:366-77 pubmed publisher
    ..Rather, it represents a less well-conserved layer of sequence organization within these sequences. ..
  25. Lucini C, D angelo L, Patruno M, Mascarello F, De Girolamo P, Castaldo L. GDNF family ligand RET receptor in the brain of adult zebrafish. Neurosci Lett. 2011;502:214-8 pubmed publisher
    b>RET is a tyrosine kinase receptor, and transduces signaling by family of glial cell line-derived neurotrophic factor ligands (GFLs)...
  26. Holzschuh J, Barrallo Gimeno A, Ettl A, Durr K, Knapik E, Driever W. Noradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and require tfap2a for expression of the neurotransmitter phenotype. Development. 2003;130:5741-54 pubmed
    ..Thus, although the inductive signals may be distinct, hindbrain NA neurons of the locus coeruleus and the posterior groups both require Tfap2a to establish their noradrenergic identity. ..
  27. Goodman K, Kjær S, Beuron F, Knowles P, Nawrotek A, Burns E, et al. RET recognition of GDNF-GFRα1 ligand by a composite binding site promotes membrane-proximal self-association. Cell Rep. 2014;8:1894-1904 pubmed publisher
    The RET receptor tyrosine kinase is essential to vertebrate development and implicated in multiple human diseases...
  28. Gabreski N, Vaghasia J, Novakova S, McDonald N, Pierchala B. Exon Skipping in the RET Gene Encodes Novel Isoforms That Differentially Regulate RET Protein Signal Transduction. J Biol Chem. 2016;291:16249-62 pubmed publisher
    Rearranged during transfection (RET), a receptor tyrosine kinase that is activated by the glial cell line-derived neurotrophic factor family ligands (GFLs), plays a crucial role in the development and function of the nervous system and ..
  29. Bisgrove B, Raible D, Walter V, Eisen J, Grunwald D. Expression of c-ret in the zebrafish embryo: potential roles in motoneuronal development. J Neurobiol. 1997;33:749-68 pubmed
    We have isolated and characterized the zebrafish ortholog of c-ret, a gene essential for renal organogenesis and enteric nervous system development in mammals...
  30. Lam P, Kamei C, Mangos S, Mudumana S, Liu Y, Drummond I. odd-skipped related 2 is required for fin chondrogenesis in zebrafish. Dev Dyn. 2013;242:1284-92 pubmed publisher
    ..The zebrafish odd-skipped related 2 gene regulates sox9a and col2a1 expression in chondrocyte development and is specifically required for zebrafish fin morphogenesis. ..
  31. Sheehan Rooney K, Swartz M, Zhao F, Liu D, Eberhart J. Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR). Dis Model Mech. 2013;6:1285-91 pubmed publisher
    ..The strengths of the zebrafish system, including rapid development, genetic tractability and live imaging, make this an important model for variability. ..
  32. Luo R, An M, Arduini B, Henion P. Specific pan-neural crest expression of zebrafish Crestin throughout embryonic development. Dev Dyn. 2001;220:169-74 pubmed
    ..Expression of crestin is gradually downregulated in overtly differentiated cells. Our results indicate that crestin is a specific pan-neural crest marker throughout zebrafish embryogenesis. ..
  33. Burckle C, Gaudé H, Vesque C, Silbermann F, Salomon R, Jeanpierre C, et al. Control of the Wnt pathways by nephrocystin-4 is required for morphogenesis of the zebrafish pronephros. Hum Mol Genet. 2011;20:2611-27 pubmed publisher
    ..Moreover, they highlight common signalling functions for inversin and nephrocystin-4, suggesting that these two nephrocystins are involved in common physiopathological mechanisms. ..
  34. Vasilyev A, Liu Y, Mudumana S, Mangos S, Lam P, Majumdar A, et al. Collective cell migration drives morphogenesis of the kidney nephron. PLoS Biol. 2009;7:e9 pubmed publisher
    ..of the nephron was, however, accompanied by an increase in tubule cell number, specifically in the most distal, ret1-positive nephron segment. The initiation of cell migration coincided with the onset of fluid flow in the pronephros...
  35. Heanue T, Pachnis V. Ret isoform function and marker gene expression in the enteric nervous system is conserved across diverse vertebrate species. Mech Dev. 2008;125:687-99 pubmed publisher
    ..Mutations in the RET tyrosine kinase account for over half of familial cases of HSCR and mice mutant for Ret exhibit aganglionosis...
  36. Ma M, Jiang Y. Jagged2a-notch signaling mediates cell fate choice in the zebrafish pronephric duct. PLoS Genet. 2007;3:e18 pubmed
    ..Taken together, our findings add a new paradigm of Notch signaling in kidney development, namely, that Jagged2a-Notch signaling modulates cell fate choice in a nephric segment, the distal pronephric duct. ..
  37. Elworthy S, Pinto J, Pettifer A, Cancela M, Kelsh R. Phox2b function in the enteric nervous system is conserved in zebrafish and is sox10-dependent. Mech Dev. 2005;122:659-69 pubmed
    ..However, in addition, we trace back the sox10 mutant ENS defect to an even earlier time point, finding that most neural crest cells fail to migrate ventrally to the gut primordium. ..
  38. Shepherd I, Beattie C, Raible D. Functional analysis of zebrafish GDNF. Dev Biol. 2001;231:420-35 pubmed
    ..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. ..
  39. Pu J, Tang S, Tong Q, Wang G, Jia H, Jia Q, et al. Neuregulin 1 is involved in enteric nervous system development in zebrafish. J Pediatr Surg. 2017;52:1182-1187 pubmed publisher
    ..In addition, by modulating NRG1 expression, we created a model that may be useful for investigating the mechanism underlying HD pathogenesis. ..
  40. Kelsh R, Eisen J. The zebrafish colourless gene regulates development of non-ectomesenchymal neural crest derivatives. Development. 2000;127:515-25 pubmed
    ..The combination of pigmentation and enteric nervous system defects makes colourless mutations a model for two human neurocristopathies, Waardenburg-Shah syndrome and Hirschsprung's disease. ..