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Stem Cells International
Volume 2016, Article ID 9076823, 12 pages
Research Article

Expression of the Wnt Receptor Frizzled-4 in the Human Enteric Nervous System of Infants

1Institute of Clinical Anatomy and Cell Analysis, University of Tübingen, Tübingen, Germany
2Department of Pediatric Surgery and Pediatric Urology, University Children’s Hospital Tübingen, Tübingen, Germany
3Division of Hematology, Immunology, Oncology, Rheumatology and Pulmonology, Department of Internal Medicine II, University of Tübingen, Tübingen, Germany
4Institute for Pathology and Neuropathology, Department of Neuropathology, University of Tübingen, Tübingen, Germany

Received 15 May 2015; Accepted 12 July 2015

Academic Editor: Kodandaramireddy Nalapareddy

Copyright © 2016 Katharina Nothelfer 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 Wnt signalling pathway plays a crucial role in the development of the nervous system. This signalling cascade is initiated upon binding of the secreted Wnt ligand to a member of the family of frizzled receptors. In the present study, we analysed the presence of frizzled-4 in the enteric nervous system of human infants. Frizzled-4 could be identified by immunohistochemistry in a subpopulation of enteric neuronal and glial cells in the small and large intestine. Detection of frizzled-4 in the tunica muscularis by RT-PCR confirmed this receptor’s expression on the mRNA level. Interestingly, we observed distinct cell populations that co-expressed frizzled-4 with the intermediate filament protein nestin and the neurotrophin receptor , which have been reported to be expressed in neural progenitor cells. Flow cytometry analysis revealed that 60% of positive cells of the tunica muscularis were positive for frizzled-4. Additionally, in pathological samples of Hirschsprung’s disease, the expression of this Wnt receptor correlated with the number of myenteric ganglion cells and decreased from normoganglionic to aganglionic areas of large intestine. The expression pattern of frizzled-4 indicates that this Wnt receptor could be involved in postnatal development and/or function of the enteric nervous system.