|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
doi: 10.1242/10.1242/dev.00433
1 Departments of Pediatrics and Molecular Biology and Pharmacology, Washington
University School of Medicine, St Louis, MO 63110, USA
2 Departments of Pathology and Internal Medicine, Washington University School
of Medicine, St Louis, MO 63110, USA
3 Departments of Physiology and Medicine, Medical College of Virginia of
Virginia Commonwealth University, Richmond, VA 23298, USA
4 Laboratory for Neuronal Differentiation and Regeneration, RIKEN Center for
Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo
650-0047 Japan
* Author for correspondence (e-mail: heuckeroth{at}kids.wustl.edu)
Accepted 10 February 2003
To clarify the role of Ret signaling components in enteric nervous system
(ENS) development, we evaluated ENS anatomy and intestinal contractility in
mice heterozygous for Ret, GFR
1 and Ret ligands. These analyses
demonstrate that glial cell line-derived neurotrophic factor (GDNF) and
neurturin are important for different aspects of ENS development. Neurturin is
essential for maintaining the size of mature enteric neurons and the extent of
neuronal projections, but does not influence enteric neuron number. GDNF
availability determines enteric neuron number by controlling ENS precursor
proliferation. However, we were unable to find evidence of programmed cell
death in the wild type ENS by immunohistochemistry for activated caspase 3. In
addition, enteric neuron number is normal in
Bax–/– and
Bid–/– mice, suggesting that, in contrast to
most of the rest of the nervous system, programmed cell death is not important
for determining enteric neuron numbers. Only mild reductions in neuron size
and neuronal fiber counts occur in Ret+/– and
Gfra1+/– mice. All of these heterozygous mice,
however, have striking problems with intestinal contractility and
neurotransmitter release, demonstrating that Ret signaling is critical for
both ENS structure and function.
Key words: GDNF, ENS, Apoptosis, Ret, Neurons, Mouse
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  A. J. Barlow, A. S. Wallace, N. Thapar, and A. J. Burns Critical numbers of neural crest cells are required in the pathways from the neural tube to the foregut to ensure complete enteric nervous system formation Development, May 1, 2008; 135(9): 1681 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Roberts, J. C. Bornstein, A. J. Bergner, and H. M. Young Disturbances of colonic motility in mouse models of Hirschsprung's disease Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G996 - G1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. S. Vohra, M. Fu, and R. O. Heuckeroth Protein Kinase C{zeta} and Glycogen Synthase Kinase-3{beta} Control Neuronal Polarity in Developing Rodent Enteric Neurons, whereas SMAD Specific E3 Ubiquitin Protein Ligase 1 Promotes Neurite Growth But Does Not Influence Polarity J. Neurosci., August 29, 2007; 27(35): 9458 - 9468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. D'Autreaux, Y. Morikawa, P. Cserjesi, and M. D. Gershon Hand2 is necessary for terminal differentiation of enteric neurons from crest-derived precursors but not for their migration into the gut or for formation of glia Development, June 15, 2007; 134(12): 2237 - 2249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Uesaka, S. Jain, S. Yonemura, Y. Uchiyama, J. Milbrandt, and H. Enomoto Conditional ablation of GFR{alpha}1 in postmigratory enteric neurons triggers unconventional neuronal death in the colon and causes a Hirschsprung's disease phenotype Development, June 1, 2007; 134(11): 2171 - 2181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jain, J. P. Golden, D. Wozniak, E. Pehek, E. M. Johnson Jr, and J. Milbrandt RET Is Dispensable for Maintenance of Midbrain Dopaminergic Neurons in Adult Mice J. Neurosci., October 25, 2006; 26(43): 11230 - 11238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Bondurand, D. Natarajan, A. Barlow, N. Thapar, and V. Pachnis Maintenance of mammalian enteric nervous system progenitors by SOX10 and endothelin 3 signalling Development, May 15, 2006; 133(10): 2075 - 2086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Carniti, S. Belluco, E. Riccardi, A. N. Cranston, P. Mondellini, B. A.J. Ponder, E. Scanziani, M. A. Pierotti, and I. Bongarzone The RetC620R Mutation Affects Renal and Enteric Development in a Mouse Model of Hirschsprung's Disease Am. J. Pathol., April 1, 2006; 168(4): 1262 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Naughton, S. Jain, A. M. Strickland, A. Gupta, and J. Milbrandt Glial Cell-Line Derived Neurotrophic Factor-Mediated RET Signaling Regulates Spermatogonial Stem Cell Fate Biol Reprod, February 1, 2006; 74(2): 314 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Skinner, S. Kalyanaraman, S. D. Safford, R. O. Heuckeroth, W. Tourtellotte, D. Goyeau, P. Goodfellow, J. D. Milbrandt, and A. Freemerman A Human Yeast Artificial Chromosome Containing the Multiple Endocrine Neoplasia Type 2B Ret Mutation Does Not Induce Medullary Thyroid Carcinoma but Does Support the Growth of Kidneys and Partially Rescues Enteric Nervous System Development in Ret-Deficient Mice Am. J. Pathol., January 1, 2005; 166(1): 265 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jain, C. K. Naughton, M. Yang, A. Strickland, K. Vij, M. Encinas, J. Golden, A. Gupta, R. Heuckeroth, E. M. Johnson Jr, et al. Mice expressing a dominant-negative Ret mutation phenocopy human Hirschsprung disease and delineate a direct role of Ret in spermatogenesis Development, November 1, 2004; 131(21): 5503 - 5513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R B Anderson, H Enomoto, J C Bornstein, and H M Young The enteric nervous system is not essential for the propulsion of gut contents in fetal mice Gut, October 1, 2004; 53(10): 1546 - 1547. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Jijiwa, T. Fukuda, K. Kawai, A. Nakamura, K. Kurokawa, Y. Murakumo, M. Ichihara, and M. Takahashi A Targeting Mutation of Tyrosine 1062 in Ret Causes a Marked Decrease of Enteric Neurons and Renal Hypoplasia Mol. Cell. Biol., September 15, 2004; 24(18): 8026 - 8036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Oatley, J. J. Reeves, and D. J. McLean Biological Activity of Cryopreserved Bovine Spermatogonial Stem Cells During In Vitro Culture Biol Reprod, September 1, 2004; 71(3): 942 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fu, V. C. H. Lui, M. H. Sham, V. Pachnis, and P. K. H. Tam Sonic hedgehog regulates the proliferation, differentiation, and migration of enteric neural crest cells in gut J. Cell Biol., August 30, 2004; 166(5): 673 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Encinas, R. J. Crowder, J. Milbrandt, and E. M. Johnson Jr. Tyrosine 981, a Novel Ret Autophosphorylation Site, Binds c-Src to Mediate Neuronal Survival J. Biol. Chem., April 30, 2004; 279(18): 18262 - 18269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Oatley, D. M. de Avila, J. J. Reeves, and D. J. McLean Testis Tissue Explant Culture Supports Survival and Proliferation of Bovine Spermatogonial Stem Cells Biol Reprod, March 1, 2004; 70(3): 625 - 631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. T. Shepherd, J. Pietsch, S. Elworthy, R. N. Kelsh, and D. W. Raible Roles for GFR{alpha}1 receptors in zebrafish enteric nervous system development Development, January 1, 2004; 131(1): 241 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Bondurand, D. Natarajan, N. Thapar, C. Atkins, and V. Pachnis Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from foetal and postnatal gut cultures Development, December 22, 2003; 130(25): 6387 - 6400. [Abstract] [Full Text] [PDF]
|
|
