Yang, Jiwen and Bücker, Sandra and Jungblut, Benno and Böttger, Thomas and Cinnamon, Yuval and Tchorz, Jan and Müller, Matthias and Bettler, Bernhard and Harvey, Richard P and Sun, Qing-Yuan and Schneider, Andre and Braun, Thomas (2012) Inhibition of Notch2 by Numb/Numblike controls myocardial compaction in the heart. Cardiovascular research, 96 (2). pp.276-85. ISSN 1755-3245 (OA)
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Abstract
AIMS
The ventricular wall of the heart is composed of trabeculated and compact layers, which are separated by yet unknown processes during embryonic development. Here, we wanted to explore the role of Notch2 and Numb/Numblike for myocardial trabeculation and compaction.
METHODS AND RESULTS
We found that Notch2 activity is specifically down-regulated in the compact layer during cardiac development in the mouse. The biological role of Notch2 down-regulation was investigated by the expression of constitutively active Notch2 in the myocardium of transgenic mice, resulting in hypertrabeculation, reduced compaction, and ventricular septum defects. To disclose the mechanism that inhibited Notch2 activity during the formation of myocardial layers, we analysed potential suppressors of Notch signalling. We unveiled that concomitant but not separate ablation of Numb and Numblike in the developing heart leads to increased Notch2 activity along with hypertrabeculation, reduced compaction, and ventricular septum defects, phenocopying effects gained by overexpression of constitutively active Notch2. Expression profiling revealed a strong up-regulation of Bmp10 in Numb/Numblike mutant hearts, which might also interfere with trabeculation and compaction.
CONCLUSION
This study identified potential novel roles of Numb/Numblike in regulating trabeculation and compaction by inhibiting Notch2 and Bmp10 signalling.
(No Australian funders listed).
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 11 Jan 2016 05:06 |
| Last Modified: | 22 Jan 2016 00:28 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/161 |
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