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Status |
Public on Aug 01, 2010 |
Title |
BMP-mediated inhibition of FGF signaling promotes cardiomyocyte differentiation of anterior heart field progenitors |
Organism |
Gallus gallus |
Experiment type |
Expression profiling by array
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Summary |
The transition from progenitor to differentiated cells is critical for successful organogenesis; subtle alterations in this process can lead to developmental disorders. The anterior heart field (AHF) encompasses a niche in which cardiac progenitors maintain their multipotent and undifferentiated nature by signals from the surrounding tissues, which thus far have been poorly defined. Using systems biology approaches and perturbations of signaling molecules in chick embryos, we revealed a tight crosstalk between the bone morphogenic protein (BMP) and fibroblast growth factor (FGF) signaling pathways within the AHF: BMP4 promotes myofibrillar gene expression and cardiomyocyte contractions, by blocking FGF signaling. Furthermore, inhibition of the FGF-ERK pathway is both sufficient and necessary for these processes, suggesting that FGF signaling blocks premature differentiation of cardiac progenitors in the AHF. Investigating the molecular mechanisms downstream to BMP signaling revealed that BMP4 induced a set of neural crest-related genes; including MSX1, which was sufficient to induce cardiomyocyte differentiation. We suggest that BMP and FGF signaling pathways act via inter- and intra-regulatory loops in multiple tissues, to coordinate the balance between proliferation and differentiation of cardiac progenitors.
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Overall design |
Splanchnic mesoderm (AHF) explants were dissected and cultured for 0, 3, 12 or 24 hrs on a collagen drop covered with 0.5 ml of dissection medium (10% Fetal Calf Serum, chick embryo extract 2.5% and pen/strep 0.5% in MEM medium). 12 hour time point was used as a duplicate. In all samples, there was control plus BMP4: human recombinant BMP4 (Sigma, 200 ng/mL), which was added to the explant dissection medium.
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Contributor(s) |
Tirosh-Finkel L, Zeisel A, Brodt-Ivenshitz M, Shamai A, Yao Z, Seger R, Domany E, Tzahor E |
Citation(s) |
20702560 |
Submission date |
Dec 29, 2009 |
Last update date |
Mar 21, 2012 |
Contact name |
Amit Zeisel |
E-mail(s) |
amit.zeisel@weizmann.ac.il
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Organization name |
Weizmann Institute of Science
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Department |
Physics of complex systems
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Lab |
Prof. Eytan Domany
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Street address |
Weizmann Institute
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City |
Rehovot |
ZIP/Postal code |
76100 |
Country |
Israel |
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Platforms (1) |
GPL3213 |
[Chicken] Affymetrix Chicken Genome Array |
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Samples (9)
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GSM491634 |
untreated AHF explants |
GSM491635 |
untreated AHF explants 3hr after plating |
GSM491636 |
untreated AHF explants 12hr after plating, A |
GSM491637 |
untreated AHF explants 12hr after plating, B |
GSM491638 |
untreated AHF explants 24hr after plating |
GSM491639 |
BMP4 treated AHF explants 3hr after plating |
GSM491640 |
BMP4 treated AHF explants 12hr after plating, A |
GSM491641 |
BMP4 treated AHF explants 12hr after plating, B |
GSM491642 |
BMP4 treated AHF explants 24hr after plating |
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Relations |
BioProject |
PRJNA121875 |
Supplementary file |
Size |
Download |
File type/resource |
GSE19698_RAW.tar |
31.6 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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