Neural cells in the esophagus respond to glial cell line-derived neurotrophic factor and neurturin, and are RET-dependent

• Published in: Developmental biology 2004-08, Vol.272 (1), p.118-133
• Main Authors: Yan, Hui, Bergner, Annette J, Enomoto, Hideki, Milbrandt, Jeffrey, Newgreen, Donald F, Young, Heather M
• Format: Article
• Language: English
• Subjects: Animals; Cell Division; Cell migration; Cell Movement - drug effects; Digestive System - cytology; Digestive System - drug effects; Digestive System - embryology; Esophagus; Esophagus - cytology; Esophagus - drug effects; Esophagus - embryology; Female; Gastrointestinal tract; GDNF; Glial Cell Line-Derived Neurotrophic Factor; Glial Cell Line-Derived Neurotrophic Factor Receptors; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Nerve Growth Factors - pharmacology; Nerve Tissue Proteins - pharmacology; Neural Crest - cytology; Neural Crest - drug effects; Neurite outgrowth; Neurites - drug effects; Neurons - cytology; Neurons - drug effects; Neurturin; Organ Culture Techniques - methods; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Nerve Growth Factor - metabolism; Ret
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2004.04.025

Glial cell line-derived neurotrophic factor (GDNF) is expressed in the gastrointestinal tract of the developing mouse and appears to play an important role in the migration of enteric neuron precursors into and along the small and large intestines. Two other GDNF family members, neurturin and artemin, are also expressed in the developing gut although artemin is only expressed in the esophagus. We examined the effects of GDNF, neurturin, and artemin on neural crest cell migration and neurite outgrowth in explants of mouse esophagus, midgut, and hindgut. Both GDNF and neurturin induced neural crest cell migration and neurite outgrowth in all regions examined. In the esophagus, the effect of GDNF on migration and neurite outgrowth declined with age between E11.5 and E14.5, but neurturin still had a strong neurite outgrowth effect at E14.5. Artemin did not promote neural migration or neurite outgrowth in any region investigated. The effects of GDNF family ligands are mediated by the Ret tyrosine kinase. We examined the density of neurons in the esophagus of Ret −/− mice, which lack neurons in the small and large intestines. The density of esophageal neurons in Ret −/− mice was only about 4% of the density of esophageal neurons in Ret +/− and Ret +/+ mice. These results show that GDNF and neurturin promote migration and neurite outgrowth of crest-derived cells in the esophagus as well as the intestine. Moreover, like intestinal neurons, the development of esophageal neurons is largely Ret-dependent.