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Gdnf is mitogenic, neurotrophic, and chemoattractive to enteric neural crest cells in the embryonic colon

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  • Olive Mwizerwa
  • Pragnya Das
  • Nandor Nagy
  • Sophia E Akbareian
  • John D Mably
  • Allan M Goldstein

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http://onlinelibrary.wiley.com/doi/10.1002/dvdy.22630/abstract
Original languageEnglish
Pages (from-to)1402-1411
Number of pages10
JournalDevelopmental Dynamics
Volume240
Issue number6
DOIs
Publication statusPublished - Jun 2011

Abstract

Glial-derived neurotrophic factor (Gdnf) is required for morphogenesis of the enteric nervous system (ENS) and it has been shown to regulate proliferation, differentiation, and survival of cultured enteric neural crest-derived cells (ENCCs). 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-mediated gene overexpression and retroviral vector-based gene silencing. We find that Gdnf has a pleiotropic effect on colonic ENCCs, promoting proliferation, inducing neuronal differentiation, and acting as a chemoattractant. Down-regulating 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.

    Research areas

  • Animals, Animals, Genetically Modified, Chemotaxis, Chick Embryo, Colon, Enteric Nervous System, Genetic Vectors, Glial Cell Line-Derived Neurotrophic Factor, Mitogens, Mitosis, Neural Crest, Neurons, Retroviridae, Signal Transduction, enteric nervous system, glial-derived neurotrophic factor, Gdnf, Ret, Hirschsprung's disease, chick

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