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BioMed Research International
Volume 2014, Article ID 328348, 7 pages
Research Article

New Insights into c-Ret Signalling Pathway in the Enteric Nervous System and Its Relationship with ALS

1Department of Human Anatomy and Histology, Faculty of Medicine, University of Zaragoza, Domingo Miral, s/n, 50009 Zaragoza, Spain
2Aragon Health Sciences Institute (I+CS), Zaragoza, Spain
3Department of Cellular Biology, Physiology and Immunology, Faculty of Medicine, University of Córdoba, Spain
4Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Spain
5Department of Obstetrics, Gynaecology and Surgery, University of Zaragoza, Spain
6Department Pharmacology and Physiology, Faculty of Medicine, University of Zaragoza, Spain

Received 23 January 2014; Accepted 7 April 2014; Published 28 April 2014

Academic Editor: Ana Cristina Calvo

Copyright © 2014 M. J. Luesma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The receptor tyrosine kinase Ret (c-Ret) transduces the glial cell line-derived neurotrophic factor (GDNF) signal, one of the neurotrophic factors related to the degeneration process or the regeneration activity of motor neurons in amyotrophic lateral sclerosis (ALS). The phosphorylation of several tyrosine residues of c-Ret seems to be altered in ALS. c-Ret is expressed in motor neurons and in the enteric nervous system (ENS) during the embryonic period. The characteristics of the ENS allow using it as model for central nervous system (CNS) study and being potentially useful for the research of human neurological diseases such as ALS. The aim of the present study was to investigate the cellular localization and quantitative evaluation of marker c-Ret in the adult human gut. To assess the nature of c-Ret positive cells, we performed colocalization with specific markers of cells that typically are located in the enteric ganglia. The colocalization of PGP9.5 and c-Ret was preferentially intense in enteric neurons with oval morphology and mostly peripherally localized in the ganglion, so we concluded that the c-Ret receptor is expressed by a specific subtype of enteric neurons in the mature human ENS of the gut. The functional significance of these c-Ret positive neurons is discussed.