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FP5

GDNF Report Summary

Project ID: QLG3-CT-2002-01000
Funded under: FP5-LIFE QUALITY
Country: United Kingdom

ENS progenitors are co-ordinately controlled by the endothelin receptor EDNRB and the GDNF receptor RET

Two signalling systems mediated by RET and EDNRB have been identified as critical players in enteric neurogenesis. We have demonstrated that interaction between these signalling pathways controls ENS development throughout the intestine. Activation of EDNRB specifically enhanced the effect of RET signalling on the proliferation of uncommitted ENS progenitors. In addition, we found novel antagonistic roles of these pathways on the migration of ENS progenitors. Protein kinase A was a key component of the molecular mechanisms that integrate signalling by the two receptors. These data provide strong evidence that the coordinate and balanced interaction between receptor tyrosine kinases and G protein-coupled receptors controls the development of the nervous system in mammals.

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John WILLS
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