GDNF Is a Chemoattractant for Enteric Neural Cells

• Published in: Developmental biology Vol. 229; no. 2; pp. 503 - 516
• Main Authors: Young, H.M., Hearn, C.J., Farlie, P.G., Canty, A.J., Thomas, P.Q., Newgreen, D.F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-01-2001
• Subjects: Animals; axon growth; Cecum - embryology; Cecum - innervation; Cell Division - drug effects; chemoattraction; dorsal root ganglion; Embryonic and Fetal Development; enteric nervous system; Enteric Nervous System - embryology; Gene Expression Regulation, Developmental; Glial Cell Line-Derived Neurotrophic Factor; Intestines - embryology; Intestines - innervation; Mice; migration; Nerve Growth Factors - genetics; Nerve Growth Factors - pharmacology; Nerve Growth Factors - physiology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - pharmacology; Nerve Tissue Proteins - physiology; neural crest; Neurons - cytology; Neurons - drug effects; Neurons - physiology; Organ Culture Techniques; RNA, Messenger - genetics; sympathetic; Transcription, Genetic; sympathetic; neural crest; axon growth; dorsal root ganglion; migration; enteric nervous system; chemoattraction
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1006/dbio.2000.0100

In situ hybridization revealed that GDNF mRNA in the mid- and hindgut mesenchyme of embryonic mice was minimal at E10.5 but was rapidly elevated at all gut regions after E11, but with a slight delay (0.5 days) in the hindgut. GDNF mRNA expression was minimal in the mesentery and in the pharyngeal and pelvic mesenchyme adjacent to the gut. To examine the effect of GDNF on enteric neural crest-derived cells, segments of E11.5 mouse hindgut containing crest-derived cells only at the rostral ends were attached to filter paper supports and grown in catenary organ culture. With GDNF (100 ng/ml) in the culture medium, threefold fewer neurons developed in the gut explants and fivefold more neurons were present on the filter paper outside the gut explants, compared to controls. Thus, in controls, crest-derived cells colonized the entire explant and differentiated into neurons, whereas in the presence of exogenous GDNF, most crest-derived cells migrated out of the gut explant. This is consistent with GDNF acting as a chemoattractant. To test this idea, explants of esophagus, midgut, superior cervical ganglia, paravertebral sympathetic chain ganglia, or dorsal root ganglia from E11.5–E12.5 mice were grown on collagen gels with a GDNF-impregnated agarose bead on one side and a control bead on the opposite side. Migrating neural cells and neurites from the esophagus and midgut accumulated around the GDNF-impregnated beads, but neural cells in other tissues showed little or no chemotactic response to GDNF, although all showed GDNF-receptor (Ret and GFRα1) immunoreactivity. We conclude that GDNF may promote the migration of crest cells throughout the gastrointestinal tract, prevent them from straying out of the gut (into the mesentery and pharyngeal and pelvic tissues), and promote directed axon outgrowth.