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The goal of this study was to investigate its in vivo role in the colon, the site most commonly affected by intestinal neuropathies such as Hirschsprung's disease. Gdnf activity was modulated in ovo in the distal gut of avian embryos using targeted retrovirus\u2010mediated gene overexpression and retroviral vector\u2010based gene silencing. We find that Gdnf has a pleiotropic effect on colonic ENCCs, promoting proliferation, inducing neuronal differentiation, and acting as a chemoattractant. Down\u2010regulating Gdnf similarly induces premature neuronal differentiation, but also inhibits ENCC proliferation, leading to distal colorectal aganglionosis with severe proximal hypoganglionosis. These results indicate an important role for Gdnf signaling in colonic ENS formation and emphasize the critical balance between proliferation and differentiation in the developing ENS. Developmental Dynamics 240:1402\u20131411, 2011. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.22630","type":"journal-article","created":{"date-parts":[[2011,4,4]],"date-time":"2011-04-04T12:35:17Z","timestamp":1301920517000},"page":"1402-1411","source":"Crossref","is-referenced-by-count":52,"title":["Gdnf is mitogenic, neurotrophic, and chemoattractive to enteric neural crest cells in the embryonic colon"],"prefix":"10.1002","volume":"240","author":[{"given":"Olive","family":"Mwizerwa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pragnya","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandor","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia 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