TY - JOUR
T1 - Abrogation of prostaglandin E2/EP4 signaling impairs the development of rag1+ lymphoid precursors in the thymus of zebrafish embryos
AU - Villablanca, Eduardo J.
AU - Pistocchi, Anna
AU - Court, Felipe A.
AU - Cotelli, Franco
AU - Bordignon, Claudio
AU - Allende, Miguel L.
AU - Traversari, Catia
AU - Russo, Vincenzo
PY - 2007/7/1
Y1 - 2007/7/1
N2 - PGE2 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 PGE2 during T cell development in zebraflsh. In this study, we show that zebraflsh ep4a, a PGE2 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 PGE2 results in a strong increase in rag1 levels and cell proliferation in the thymus. In contrast, the inhibition of PGE2 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 (sc1, gata2) and erythropoietic (gata1) markers. These results identify ep4a as the earliest thymus marker and define a novel role for the PGE2/EP4 pathway in controlling T cell precursor development in zebraflsh.
AB - PGE2 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 PGE2 during T cell development in zebraflsh. In this study, we show that zebraflsh ep4a, a PGE2 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 PGE2 results in a strong increase in rag1 levels and cell proliferation in the thymus. In contrast, the inhibition of PGE2 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 (sc1, gata2) and erythropoietic (gata1) markers. These results identify ep4a as the earliest thymus marker and define a novel role for the PGE2/EP4 pathway in controlling T cell precursor development in zebraflsh.
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M3 - Article
C2 - 17579056
AN - SCOPUS:34250889280
VL - 179
SP - 357
EP - 364
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -