First published online May 16, 2007
Development 134, 1102e (2007)
© The Company of Biologists Limited
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 GFR
1, 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.
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]
