Document Detail

Inhibition of Notch2 by Numb/Numblike controls myocardial compaction in the heart.
MedLine Citation:
PMID:  22865640     Owner:  NLM     Status:  Publisher    
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 ResultsWe found that Notch2 activity is specifically downregulated in the compact layer during cardiac development of the mouse. The biological role of Notch2 downregulation was investigated by 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 formation of myocardial layers, we analyzed potential suppressors of Notch signaling. 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 upregulation of Bmp10 in Numb/Numblike mutant hearts, which might also interfere with trabeculation and compaction. CONCLUSIONS: This study identified potential novel roles of Numb/Numblike in regulating trabeculation and compaction by inhibiting Notch2 and Bmp10 signaling.
Jiwen Yang; Sandra Bücker; Benno Jungblut; Thomas Böttger; Yuval Cinnamon; Jan Tchorz; Matthias Müller; Bernhard Bettler; Richard Harvey; Qing-Yuan Sun; Andre Schneider; Thomas Braun
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-3
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodelling, Bad Nauheim, Germany.
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