Abstract
Glial-derived neurotrophic factor (GDNF), neurturin (NRTN), persephin (PSPN), and artemin (ARTN) are a group of proteins belonging to the GDNF family ligands (GFLs). GDNF, NRTN, and ARTN support the survival of central, peripheral, and autonomic neuron populations, while PSPN supports the survival of only several central neuron populations. A common receptor, RET, modulates the action of this family and a co-receptor, GFRα, determines RET ligand specificity. GDNF and NRTN appear to be essential for enteric nervous system (ENS) development in mammals, zebrafish, and other teleostean species. GFLs are also essential for the maintenance and plasticity of adult mammalian ENS. In this study, the distribution pattern of GFLs in the intestine of five adult fish (bass, gilt-head, scorpionfish, trout, and zebrafish) was evaluated by immunochemical and immunocytochemical analysis. The results demonstrated the presence of GDNF, NRTN, and ARTN in the gut of all species studied. They appeared to be spread in the ENS and/or endocrine cells of the intestine. These findings suggest that the presence of GFLs in fish gut is not only limited to developmental period, but could be also involved in the enteric physiology of adult species.
Similar content being viewed by others
References
Airaksinen MS, Saarma M (2002) The GDNF family: signalling, biological functions and therapeutic value. Nat Rev 3:383–394
Baloh RH, Tansey MG, Lampe PA, Fahrner TJ, Enomoto H, Simburger KS, Leitner ML, Araki T, Johnson EM Jr, Millbrandt J (1998) Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRα3-RET receptor complex. Neuron 21:1291–1302
Belluardo N, Mudo G, Caniglia G, Corsaro M, Cheng Q, Frasca F, Belfiore A, Condorelli DF (1999) Expression of neurotrophins, GDNF, and their receptors in rat thyroid tissue. Cell Tissue Res 295:467–475
Chalazonitis A, Rothman TP, Chen J, Gershon MD (1998) Age-dependent differences in the effects of GDNF and NT-3 on the development of neurons and glia from neural crest-derived precursors immunoselected from the fetal rat gut: expression of GFRalpha-1 in vitro and in vivo. Dev Biol 204:385–406
de Girolamo P, Lucini C, Vega JA, Andreozzi G, Coppola L, Castaldo L (1999) Co-localization of Trk neurotrophin receptors and regulatory peptides in the endocrine cells of the teleostean stomach. Anat Rec 256:219–226
Enomoto H, Araki T, Jackman A, Heuckeroth RO, Snider WD, Johnson EM Jr, Milbrandt J (1998) GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys. Neuron 21:317–324
Forander P, Broberger C, Stromberg I (2001) Glial-cell-line-derived neurotrophic factor induces nerve fibre formation in primary cultures of adrenal chromaffin cells. Cell Tissue Res 305:43–51
Franke B, Figiel M, Engele J (1998) CNS glia are targets for GDNF and neurturin. Histochem Cell Biol 110:595–601
Furness JB, Kunze WA, Clerc N (1999) Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune responses. Am J Physiol 277:G922–G928
Gianino S, Grider JR, Cresswell J, Enomoto H, Heuckeroth RO (2003) GDNF availability determines enteric neuron number by controlling precursor proliferation. Development 130:2187–2198
Golden JP, DeMaro JA, Osborne PA, Milbrandt J, Johnson EM Jr (1999) Expression of neurturin, GDNF, and GDNF family-receptor mRNA in the developing and mature mouse. Exp Neurol 158:504–528
Hannestad J, Marino F, Germana A, Catania S, Abbate F, Ciriaco E, Vega JA (2000) Trk neurotrophin receptor-like proteins in the teleost Dicentrarchus labrax. Cell Tissue Res 300:1–9
Hearn CJ, Murphy M, Newgreen D (1998) GDNF and ET-3 differentially modulate the numbers of avian enteric neural crest cells and enteric neurons in vitro. Dev Biol 197:93–105
Heuckeroth RO, Enomoto H, Grider JR, Golden JP, Hanke JA, Jackman A, Molliver DC, Bardgett ME, Snider WD, Johnson EM Jr, Milbrandt J (1999) Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons. Neuron 22:253–263
Heuckeroth RO, Lampe PA, Johnson EM, Millbrandt J (1998) Neurturin and GDNF promote proliferation and survival of enteric neuron and glial progenitors in vitro. Dev Biol 200:116–129
Ichihara M, Murakumo Y, Takahashi M (2004) RET and neuroendocrine tumors. Cancer Lett 204:197–211
Jain S, Naughton CK, Yang M, Strickland A, Vij K, Encinas M, Golden J, Gupta A, Heuckeroth R, Johnson EM Jr, Milbrandt J (2004) Mice expressing a dominant-negative Ret mutation phenocopy human Hirschsprung disease and delineate a direct role of Ret in spermatogenesis. Development 131:5503–5513
Kotzbauer PT, Lampe PA, Heuckeroth RO, Golden JP, Creedon DJ, Johnson EM, Milbrandt J (1996) Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 384:467–470
Krieglstein K, Deimling F, Suter-Crazzolara C, Unsicker K (1996) Expression and localization of GDNF in developing and adult adrenal chromaffin cells. Cell Tissue Res 286:263–268
Lin L-FH, Doherty DH, Lile JD, Bektesh S, Collins F (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260:1130–1132
Lindahl M, Poteryaev D, Yu L, Arumae U, Timmusk T, Bongarzone I, Aiello A, Pierotti MA, Airaksinen MS, Saarma M (2001) Human glial cell line-derived neurotrophic factor receptor alpha 4 is the receptor for persephin and is predominantly expressed in normal and malignant thyroid medullary cells. J Biol Chem 276:9344–9351
Lucini C, De Girolamo P, Maruccio L, Lamanna C, Castaldo l, Vega JA (1999) Trk-neurotrophin receptor-like immunoreactivity in the gut of teleost species. Cell Tissue Res 296:323–330
Lucini C, Maruccio L, Arcamone N, Lamanna C, Castaldo L (2003) Neurotrophin-like immunoreactivity in the gut of teleost species. Neurosci Lett 345:33–36
Lucini C, Maruccio L, Tafuri S, Staiano N, Castaldo L (2004) Artemin-like immunoreactivity in the zebrafish, Danio rerio. Anat Embryol 208:403–410
Milbrandt J, de Sauvage FJ, Fahrner TJ, Baloh RH, Leitner ML, Tansey MG, Lamoe PA, Heuckeroth RO, Kotzbauer PT, Simburger KS, Golden JP, Davies JA, Vejsada R, Kato AC, Hynes M, Sherman D, Nishimura M, Wang LC, Vandlen R, Moffat B, Klein RD, Poulsen K, Gray C, Garces A, Henderson CE, Phillips HS, Johnson EM Jr (1998) Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron 20:245–253
Moore MW, Klein RD, Farinas I, Sauer H, Armanini M, Phillips H, Reichardt LF, Ryan AM, Carver-Moore K, Rosenthal A (1996) Renal and neuronal abnormalities in mice lacking GDNF. Nature 382:76–79
Natarajan D, Marcos-Gutierrez C, Pachnis V, de Graaff E (2002) Requirement of signalling by receptor tyrosine kinase RET for the directed migration of enteric nervous system progenitor cells during mammalian embryogenesis. Development 129:5151–5160
Negoescu A, Labat-Moleur F, Lorimier P, Lamarcq L, Guillermet C, Chambaz E, Brambilla E (1994) F(ab) secondary antibodies: a general method for double immunolabeling with primary antisera from the same species. Efficiency control by chemiluminescence. J Histochem Cytochem 42:433–437
Ohta K, Inokuchi T, Gen E, Chang J (2001) Ultrastructural study of anterograde transport of glial cell line-derived neurotrophic factor from dorsal root ganglion neurons of rats towards the nerve terminal. Cells Tissues Organs 169:410–421
Peters RJ, Osinski MA, Hongo JA, Bennett GL, Okragly AJ, Haak-Frendscho M, Epstein ML (1998) GDNF is abundant in the adult rat gut. J Auton Nerv Syst 70:115–122
Pichel JG, Shen L, Sheng HZ, Granholm AC, Drago J, Grinberg A, Lee EJ, Huang SP, Saarma M, Hoffer BJ, Sariola H, Westphal H (1996) Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 382:73–76
Powers JF, Schelling KH, Tischler AS (2001) Chromaffin cell mitogenesis by neurturin and glial cell line-derived neurotrophic factor. Neuroscience 108:341–349
Reynolds GM, Young FI, Williams A, Rowlands DC (1994) Microwave-oven antigen retrieval applied to the immunostaining of cytopathology specimens. Cytopathology 5:345–358
Rind HB, von Bartheld CS (2002) Anterograde axonal transport of internalized GDNF in sensory and motorneurons. Neuroreport 13:659–664
Rossi J, Herzig KH, Voikar V, Hiltunen PH, Segerstrale M, Airaksinen MS (2003) Alimentary tract innervation deficits and dysfunction in mice lacking GDNF family receptor alpha2. J Clin Invest 112:707–716
Russell FD, Koishi K, Jiang Y, McLennan IS (2000) Anterograde axonal transport of glial cell line-derived neurotrophic factor and its receptors in rat hypoglossal nerve. Neuroscience 97:575–580
Saland LC, Cunningham LA, Su C, Morales M, Gaddy J (2000) Glial cell line-derived neurotrophic factor in the rat pituitary gland. Brain Res Bull 52:109–113
Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M (1996) Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382:70–73
Sariola H, Saarma M (2003) Novel functions and signalling pathways for GDNF. J Cell Sci 116:3855–3862
Schafer KH, Mestres P (1999) The GDNF-induced neurite outgrowth and neuronal survival in dissociated myenteric plexus cultures of the rat small intestine decreases postnatally. Exp Brain Res 125:447–452
Shepherd IT, Beattie CE, Raible DW (2001) Functional analysis of zebrafish GDNF. Dev Biol 231:420–435
Shepherd IT, Pietsch J, Elworthy S, Kelsh RN, Raible DW (2004) Roles for GFRalpha1 receptors in zebrafish enteric nervous system development. Development 131:241–249
Sternberger LA (1986) Immunocytochemistry. Wiley, 3rd edn. NY
Taraviras S, Marcos-Gutierrez CV, Durbec P, Jani H, Grigoriou M, Sukumaran M, Wang LC, Hynes M, Raisman G, Pachnis V (1999) Signalling by the RET receptor tyrosine kinase and its role in the development of the mammalian enteric nervous system. Development 126:2785–2797
Tomac AC, Grinberg A, Huang SP, Nosrat C, Wang Y, Borlongan C, Lin SZ, Chiang YH, Olson L, Westphal H, Hoffer BJ (2000) Glial cell line-derived neurotrophic factor receptor alpha1 availability regulates glial cell line-derived neurotrophic factor signaling: evidence from mice carrying one or two mutated alleles. Neuroscience 95:1011–1023
von Bartheld CS, Wang X, Butowt R (2001) Anterograde axonal transport, transcytosis, and recycling of neurotrophic factors: the concept of trophic currencies in neural networks. Mol Neurobiol 24:1–28
von Boyen GB, Reinshagen M, Steinkamp M, Adler G, Kirsch J (2002) Gut inflammation modulated by the enteric nervous system and neurotrophic factors. Scand J Gastroenterol 37:621–625
Wessel GM, McClay DR (1986) Two embryonic, tissue-specific molecules identified by a double-label immunofluorescence technique for monoclonal antibodies. J Histochem Cytochem 34(6):703–706
Worley DS, Pisano JM, Choi ED, Walus L, Hession CA, Cate RL, Sanicola M, Birren SJ (2000) Developmental regulation of GDNF response and receptor expression in the enteric nervous system. Development 127:4383–4393
Xian CJ, Huang BR, Zhou XF (1999) Distribution of neurturin mRNA and immunoreactivity in the peripheral tissues of adult rats. Brain Res 835:247–258
Yan H, Bergner AJ, Enomoto H, Milbrandt J, Newgreen DF, Young HM (2004) Neural cells in the esophagus respond to glial cell line-derived neurotrophic factor and neurturin, and are RET-dependent. Dev Biol 272:118–133
Young HM, Anderson RB, Anderson CR (2004) Guidance cues involved in the development of the peripheral autonomic nervous system. Auton Neurosci 112:1–14
Young HM, Hearn CJ, Farlie PG, Canty AJ, Thomas PQ, Newgreen DF (2001) GDNF is a chemoattractant for enteric neural cells. Dev Biol 229:503–516
Acknowledgements
We thank Mrs Annamaria Zollo for her skilful technical assistance. This study was supported by a grant from Università di Napoli Federico II, Polo delle Scienze e Tecnologie per la Vita, Napoli, Italy.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lucini, C., Maruccio, L., Tafuri, S. et al. GDNF family ligand immunoreactivity in the gut of teleostean fish. Anat Embryol 210, 265–274 (2005). https://doi.org/10.1007/s00429-005-0046-0
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-005-0046-0