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First published online 6 August 2008
doi: 10.1242/dev.025163

Development 135, 3007-3011 (2008)
Published by The Company of Biologists 2008
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Research Report

Non-cell-autonomous effects of Ret deletion in early enteric neurogenesis

Silvia Bogni1, Paul Trainor2, Dipa Natarajan1, Robb Krumlauf2 and Vassilis Pachnis1,*

1 Division of Molecular Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
2 Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.

* Author for correspondence (e-mail: vpachni{at}nimr.mrc.ac.uk)

Accepted 21 July 2008

SUMMARY

Neural crest cells (NCCs) form at the dorsal margin of the neural tube and migrate along distinct pathways throughout the vertebrate embryo to generate multiple cell types. A subpopulation of vagal NCCs invades the foregut and colonises the entire gastrointestinal tract to form the enteric nervous system (ENS). The colonisation of embryonic gut by NCCs has been studied extensively in chick embryos, and genetic studies in mice have identified genes crucial for ENS development, including Ret. Here, we have combined mouse embryo and organotypic gut culture to monitor and experimentally manipulate the progenitors of the ENS. Using this system, we demonstrate that lineally marked intestinal ENS progenitors from E11.5 mouse embryos grafted into the early vagal NCC pathway of E8.5 embryos colonise the entire length of the gastrointestinal tract. By contrast, similar progenitors transplanted into Ret-deficient host embryos are restricted to the proximal foregut. Our findings establish an experimental system that can be used to explore the interactions of NCCs with their cellular environment and reveal a previously unrecognised non-cell-autonomous effect of Ret deletion on ENS development.

Key words: Enteric nervous system, Neural crest, Ret


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