Expression and regulation of reelin and its receptors in the enteric nervous system.
OBJECTIVE
In the central nervous system (CNS), reelin coordinates migration and lamination of neurons and regulates synaptic plasticity, whereas its role in the enteric nervous system (ENS) remains enigmatic. Thus we determined the expression pattern and localization of reelin in the human ENS and monitored the time course of mRNA expression of the reelin signaling system in the rat intestine as well as in GDNF treated ENS cultures.


RESULTS
Reelin, its receptors and Dab1 were expressed in all intestinal layers as well as in isolated myenteric ganglia. Enteric ganglia and nerve fibers were immunoreactive for reelin which co-localized with PGP 9.5 and synaptophysin. In the rat small intestine, highest expression levels of reelin were detected at early postnatal stages. Enteric nerve cell cultures treated with GDNF showed marked up-regulation of reelin and its receptors.


CONCLUSIONS
Reelin and its receptors are strongly expressed in the human ENS. Reelin is specifically localized in enteric neurons with highest expression levels during early postnatal life as well as in neuronal network forming enteric nerve cell cultures pointing to putative functions in the differentiation and maintenance of the ENS.


METHODS
Gene expression of reelin, its receptors and Dab1 were analyzed in the human colon and isolated enteric ganglia. Co-localization of reelin with the pan-neuronal marker PGP 9.5 and the synaptic vesicle marker synaptophysin was studied by dual-label-immunocytochemistry. The time course of reelin expression was monitored in an ontogenetic study of rat intestines as well as in GDNF-treated cultures of enteric neurons.
Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany. Electronic address: m.boettner@anat.uni-kiel.de.
Martina
M
Böttner
Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Puya
P
Ghorbani
Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Jonas
J
Harde
Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Martina
M
Barrenschee
Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Ines
I
Hellwig
Department of Surgery, Städtisches Krankenhaus Kiel, Kiel, Germany.
Ilka
I
Vogel
Department of Pathology, Städtisches Krankenhaus Kiel, Kiel, Germany.
Michael
M
Ebsen
Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Eckart
E
Förster
Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Thilo
T
Wedel
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017615:Enteric Nervous System / Q000166:cytology* / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D009197:Myenteric Plexus / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013368:Submucous Plexus / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015816:Cell Adhesion Molecules, Neuronal; C115785:DAB1 protein, human; D016326:Extracellular Matrix Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D000091042:Reelin Protein; C000717129:Reln protein, rat; D016708:Synaptophysin; C482860:UCHL1 protein, human; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C469363:reelin receptor; D043222:Ubiquitin Thiolesterase; C000717127:RELN protein, human; D012697:Serine Endopeptidases
Cell culture; Enteric nervous system; Reelin; Reelin receptors; Synaptic plasticity