Neurturin and GDNF promote proliferation and survival of enteric neuron and glial progenitors in vitro.
Signaling through the c-Ret tyrosine kinase and the endothelin B receptor pathways is known to be critical for development of the enteric nervous system. To clarify the role of these receptors in enteric nervous system development, the effect of ligands for these receptors was examined on rat enteric neuron precursors in fully defined medium in primary culture. In this culture system, dividing Ret-positive cells differentiate, cluster into ganglia containing neurons and enteric glia, and create extensive networks reminiscent of the enteric plexus established in vivo. Glial cell-line-derived neurotrophic factor (GDNF) and neurturin both potently support survival and proliferation of enteric neuron precursors in this system. Addition of either neurturin or GDNF to these cultures increased the number of both neurons and enteric glia. Persephin, a third GDNF family member, shares many properties with neurturin and GDNF in the central nervous system and in kidney development. By contrast, persephin does not promote enteric neuron precursor proliferation or survival in these cultures. Endothelin-3 also does not increase the number of enteric neurons or glia in these cultures.
Department of Molecular Biology and Pharmacology, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri, 63110, USA. heuckeroth@al.kids.wustl.edu
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Heuckeroth
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Lampe
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Johnson
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Milbrandt
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D029721:Drosophila Proteins; D019334:Endothelin-3 / Q000378:metabolism; D017615:Enteric Nervous System / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D051101:Neurturin; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects*
D016895:Culture Media, Serum-Free; D029721:Drosophila Proteins; D019334:Endothelin-3; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051101:Neurturin; C495057:Nrtn protein, rat; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C495001:Ret protein, rat