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Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1
Author(s) -
RobertMoreno Àlex,
Guiu Jordi,
RuizHerguido Cristina,
López M Eugenia,
InglésEsteve Julia,
Riera Lluis,
Tipping Alex,
Enver Tariq,
Dzierzak Elaine,
Gridley Thomas,
Espinosa Lluis,
Bigas Anna
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.113
Subject(s) - biology , notch signaling pathway , haematopoiesis , embryonic stem cell , embryogenesis , microbiology and biotechnology , anatomy , ligand (biochemistry) , genetics , embryo , stem cell , signal transduction , gene , receptor
Specific deletion of Notch1 and RBPjκ in the mouse results in abrogation of definitive haematopoiesis concomitant with the loss of arterial identity at embryonic stage. As prior arterial determination is likely to be required for the generation of embryonic haematopoiesis, it is difficult to establish the specific haematopoietic role of Notch in these mutants. By analysing different Notch‐ligand‐null embryos, we now show that Jagged1 is not required for the establishment of the arterial fate but it is required for the correct execution of the definitive haematopoietic programme, including expression of GATA2 in the dorsal aorta. Moreover, successful haematopoietic rescue of the Jagged1‐null AGM cells was obtained by culturing them with Jagged1‐expressing stromal cells or by lentiviral‐mediated transduction of the GATA2 gene. Taken together, our results indicate that Jagged1‐mediated activation of Notch1 is responsible for regulating GATA2 expression in the AGM, which in turn is essential for definitive haematopoiesis in the mouse.