Article
- The EMBO Journal (2008) 27, 1886 - 1895
- doi:10.1038/emboj.2008.113
Published online: 5 June 2008
Subject Category:
Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1
Àlex Robert-Moreno1,5,a, Jordi Guiu1,5, Cristina Ruiz-Herguido1, M Eugenia López1, Julia Inglés-Esteve1, Lluis Riera1,b, Alex Tipping2, Tariq Enver2, Elaine Dzierzak3, Thomas Gridley4, Lluis Espinosa1,5 and Anna Bigas1,5
- Centre Oncologia Molecular, IDIBELL, Gran Via km 2.7 Hospitalet, Barcelona, Spain
- MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
- Department of Cell Biology and Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
- The Jackson Laboratory, Bar Harbor, ME, USA
- These authors contributed equally to this work
Correspondence to:
Anna Bigas, Centre Oncologia Molecular, IDIBELL, Gran Via Km 2.7, Hospitalet, Barcelona 08907, Spain. Tel.: +932 607 404; Fax: +932 607 426; E-mail: abigas@iro.es
aPresent address: Universitat Pompeu Fabra, Barcelona, Spain
bPresent address: Diferenciació i Cancer, Center de Regulació Genòmica (CRG-PRBB), Barcelona, Spain
Received 27 February 2008; Accepted 14 May 2008
Abstract
Specific deletion of Notch1 and RBPj
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.
Keywords:
- AGM,
- GATA2,
- haematopoiesis,
- Jagged1,
- Notch
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