Document Detail

Abrogation of prostaglandin E2/EP4 signaling impairs the development of rag1+ lymphoid precursors in the thymus of zebrafish embryos.
MedLine Citation:
PMID:  17579056     Owner:  NLM     Status:  MEDLINE    
PGE(2) is involved in a wide variety of physiological and pathological processes; however, deciphering its role in early mammalian development has been difficult due to the maternal contribution of PGE(2). To overcome this limitation we have investigated the role of PGE(2) during T cell development in zebrafish. In this study, we show that zebrafish ep4a, a PGE(2) receptor isoform of EP4, is expressed at 26 h postfertilization in the dorsal aorta-posterior cardinal vein joint region, which has a high homology with the mammal aorta-gonad-mesonephros area and where definitive hemopoiesis arises. Furthermore, it is expressed in the presumptive thymus rudiment by 48 h postfertilization. Supplementation of PGE(2) results in a strong increase in rag1 levels and cell proliferation in the thymus. In contrast, the inhibition of PGE(2) production, as well as EP4 blockade, abrogates the expression of rag1 in the thymus and that of the lymphoid precursor marker ikaros, not only in the dorsal aorta-posterior cardinal vein joint region but also in the newly identified caudal hemopoietic tissue without affecting early hemopoietic (scl, gata2) and erythropoietic (gata1) markers. These results identify ep4a as the earliest thymus marker and define a novel role for the PGE(2)/EP4 pathway in controlling T cell precursor development in zebrafish.
Eduardo J Villablanca; Anna Pistocchi; Felipe A Court; Franco Cotelli; Claudio Bordignon; Miguel L Allende; Catia Traversari; Vincenzo Russo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  179     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-20     Completed Date:  2007-08-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  357-64     Citation Subset:  AIM; IM    
Cancer Gene Therapy Unit, Cancer Immunotherapy and Gene Therapy Program, Scientific Institute H. San Raffaele, Via Olgettina 58, Milan, Italy.
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MeSH Terms
Animals, Genetically Modified
Cell Differentiation / immunology*
Cell Proliferation
Dinoprostone / antagonists & inhibitors,  physiology
Hematopoiesis / immunology
Homeodomain Proteins / biosynthesis*
Lymphocyte Subsets / cytology,  metabolism*
Lymphopoiesis / immunology
Protein Isoforms / antagonists & inhibitors,  physiology
Receptors, Prostaglandin E / antagonists & inhibitors,  physiology*
Signal Transduction / immunology*
Stem Cells / cytology,  metabolism*
Thymus Gland / cytology,  embryology,  immunology*
Up-Regulation / immunology
Zebrafish / embryology*,  immunology
Reg. No./Substance:
0/Homeodomain Proteins; 0/Protein Isoforms; 0/Receptors, Prostaglandin E; 0/prostaglandin E2 receptor, EP4 subtype; 128559-51-3/RAG-1 protein; 363-24-6/Dinoprostone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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