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Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1.
- Source :
-
The EMBO journal [EMBO J] 2008 Jul 09; Vol. 27 (13), pp. 1886-95. Date of Electronic Publication: 2008 Jun 05. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Animals
Calcium-Binding Proteins genetics
Embryo, Mammalian metabolism
GATA2 Transcription Factor metabolism
Hematopoietic Stem Cells metabolism
Intercellular Signaling Peptides and Proteins genetics
Jagged-1 Protein
Jagged-2 Protein
Membrane Proteins genetics
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mutation
Serrate-Jagged Proteins
Aorta embryology
Calcium-Binding Proteins metabolism
Hematopoiesis
Intercellular Signaling Peptides and Proteins metabolism
Membrane Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2075
- Volume :
- 27
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 18528438
- Full Text :
- https://doi.org/10.1038/emboj.2008.113