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Expression of the GDNF receptors Ret and GFRα1 in the developing avian enteric nervous system
Author(s) -
Schiltz Craig A.,
Benjamin Jason,
Epstein Miles L.
Publication year - 1999
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/(sici)1096-9861(19991115)414:2<193::aid-cne4>3.0.co;2-v
Subject(s) - glial cell line derived neurotrophic factor , biology , neural crest , enteric nervous system , gizzard , microbiology and biotechnology , proto oncogene proteins c ret , population , neurotrophic factors , receptor , medicine , endocrinology , embryo , genetics , paleontology , demography , sociology
The formation of the enteric nervous system (ENS) from neural crest‐derived cell precursors requires the growth factor glial cell line‐derived neurotrophic factor (GDNF) and the receptors Ret and GDNF family receptor alpha 1 (GFRα1). We investigated the location(s), the timing, and the extent to which these GDNF receptors appear in the population of crest‐derived precursors that form the avian ENS using immunohistochemistry and in situ hybridization. Sections and whole mounts of embryonic chick gastrointestinal tract were costained with antibodies to the receptors and to HNK‐1, a marker for crest‐derived cells. Neural crest‐derived precursors migrate through the primitive esophagus to colonize the gizzard where an extensive cellular network forms. Ret‐immunoreactivity (ir) was found in a network of cells in the gizzard at embryonic day (E)3.5. As development proceeded, Ret‐immunoreactive cells appeared at progressively more caudal positions and were present in the colon at E7.5. Costaining with Ret and HNK‐1 was performed to determine the number of Ret‐immunoreactive cells in the crest‐derived population. Ret appeared in some HNK‐1 cells in the esophagus and gizzard at embryonic day (E)3.5. During development, the number of crest cells with Ret increased in the ganglia of the gizzard and small intestine. GFRα1‐ir was also found in HNK‐1 cells in the esophagus at E3.5 but did not appear in the gizzard until E4.5. Surprisingly, the colonizing vanguard of crest‐derived cells lacked both Ret‐ and GFRα‐ir. Between E4.5 and E6.5, the fraction of HNK‐1‐positive cells expressing GFRα1 increased considerably in the foregut. Ret and GFRα1 were coexpressed in many cells at E6.5, and the number of such cells increased as development progressed. In the adult, GFRα1 and Ret were found in the neuropil of enteric ganglia. We conclude that the population of cells expressing the receptors increases during development and persists in the adult, findings that support a neurotrophic role for GDNF in the formation and maintenance of the avian ENS. J. Comp. Neurol. 414:193–211, 1999. © 1999 Wiley‐Liss, Inc.