Document Detail


Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1.
MedLine Citation:
PMID:  18528438     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Specific deletion of Notch1 and RBPjkappa 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.
Authors:
Alex Robert-Moreno; Jordi Guiu; Cristina Ruiz-Herguido; M Eugenia López; Julia Inglés-Esteve; Lluis Riera; Alex Tipping; Tariq Enver; Elaine Dzierzak; Thomas Gridley; Lluis Espinosa; Anna Bigas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-05
Journal Detail:
Title:  The EMBO journal     Volume:  27     ISSN:  1460-2075     ISO Abbreviation:  EMBO J.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-09     Completed Date:  2008-07-22     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  1886-95     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / embryology*
Calcium-Binding Proteins / genetics,  metabolism*
Embryo, Mammalian / metabolism
GATA2 Transcription Factor / metabolism
Hematopoiesis*
Hematopoietic Stem Cells / metabolism
Intercellular Signaling Peptides and Proteins / genetics,  metabolism*
Membrane Proteins / genetics,  metabolism*
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mutation
Grant Support
ID/Acronym/Agency:
MC_U137973817//Medical Research Council
Chemical
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/GATA2 Transcription Factor; 0/Gata2 protein, mouse; 0/Intercellular Signaling Peptides and Proteins; 0/Jag2 protein, mouse; 0/Membrane Proteins; 134324-36-0/Serrate proteins
Comments/Corrections

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