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First published online May 16, 2007

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Enteric neurons: different in death

The regulated death of immature neurons, in response to the absence of neurotrophic factors, is crucial to the architecture of the developing nervous system. The enteric nervous system (ENS) regulates motility, secretion and blood flow in the gastrointestinal tract. However, unlike in other areas of the developing nervous system, neuronal apoptosis has not been detected, and survival signals that prevent it have yet to be identified. Jeffrey Milbrandt's and Hideki Enomoto's laboratories (p. 2171) now report that the survival of enteric neurons depends on GFR1, a receptor for glial cell line-derived neurotrophic factor (GDNF). Using conditional GFR1 mutant mice, the authors show that during late ENS development, GFR1 inactivation induces the widespread death of enteric neurons in the distal gastrointestinal tract in a caspase-independent manner. Because Hirschsprung's disease in humans is associated with mutations in the RET receptor kinase - the signalling component of the GDNF receptor complex - it will be interesting to determine whether caspase-independent neuronal cell death underlies the etiology of this human condition.

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Related articles in Development:

Conditional ablation of GFR1 in postmigratory enteric neurons triggers unconventional neuronal death in the colon and causes a Hirschsprung's disease phenotype

Toshihiro Uesaka, Sanjay Jain, Shigenobu Yonemura, Yasuo Uchiyama, Jeffrey Milbrandt, and Hideki Enomoto
Development 2007 134: 2171-2181. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?