AJP - GI Journal of Neurophysiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 277: G262-G267, 1999;
0193-1857/99 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gershon, M. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gershon, M. D.
Vol. 277, Issue 2, G262-G267, August 1999

THEMES
Lessons From Genetically Engineered Animal Models
II. Disorders of enteric neuronal development: insights from transgenic mice*

Michael D. Gershon

Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032

Understanding the development of congenital defects of the enteric nervous system, such as Hirschsprung's disease, was, until recently, an intractable problem. The analysis of transgenic mice, however, has now led to the discovery of a number of genetic abnormalities that give rise to aganglionic congenital megacolon or neuronal intestinal dysplasia. The identification of the responsible genes has enabled the developmental actions of their protein products to be investigated, which, in turn, has made it possible to determine the causes of aganglionoses. Two models of pathogenesis have emerged. One, associated with mutations in genes encoding endothelin-3 or its receptor, endothelin B, posits the premature differentiation of migrating neural crest-derived progenitors, causing the precursor pool to become depleted before the bowel has been fully colonized. The second, associated with mutations in genes encoding glial cell line-derived neurotrophic factor (GDNF), its preferred receptor GFRalpha 1, or their signaling component, Ret, appears to deprive a GDNF-dependent common progenitor of adequate support and/or mitogenic drive. In both cases, the terminal bowel becomes aganglionic when the number of colonizing neuronal precursors is inadequate.

Hirschsprung's disease; endothelin-3; endothelin B receptor; glial cell-derived neurotrophic factor; GFRalpha 1; Ret; aganglionosis; neural crest; neuronal development

* Second in a series of invited articles on Lessons From Genetically Engineered Animal Models.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. C. McDonagh, J. Lee, A. Izzo, and P. L. Brubaker
Role of glial cell-line derived neurotropic factor family receptor {alpha}2 in the actions of the glucagon-like peptides on the murine intestine
Am J Physiol Gastrointest Liver Physiol, August 1, 2007; 293(2): G461 - G468.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
Y. Mao, B. Wang, and W. Kunze
Characterization of Myenteric Sensory Neurons in the Mouse Small Intestine
J Neurophysiol, September 1, 2006; 96(3): 998 - 1010.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
A. J. Burns, J.-M. M. Delalande, and N. M. Le Douarin
In ovo transplantation of enteric nervous system precursors from vagal to sacral neural crest results in extensive hindgut colonisation
Development, March 8, 2003; 129(12): 2785 - 2796.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. M. Ward, M. D. Gershon, K. Keef, Y. R. Bayguinov, C. Nelson, and K. M. Sanders
Interstitial cells of Cajal and electrical activity in ganglionic and aganglionic colons of mice
Am J Physiol Gastrointest Liver Physiol, August 1, 2002; 283(2): G445 - G456.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online