Please use this identifier to cite or link to this item: https://doi.org/10.1172/jci.insight.125908
Title: Semaphorin 3E/PlexinD1 Signaling Is Required for Cardiac Ventricular Compaction.
Authors: SANDIREDDY REDDEMMA 
DASAN MARY CIBI 
Gupta P
ANAMIKA SINGH 
Tee N
Uemura A
Epstein JA
Singh Manvendra Kumar 
Issue Date: 22-Aug-2019
Publisher: The American Society for Clinical Investigation
Citation: SANDIREDDY REDDEMMA, DASAN MARY CIBI, Gupta P, ANAMIKA SINGH, Tee N, Uemura A, Epstein JA, Singh Manvendra Kumar (2019-08-22). Semaphorin 3E/PlexinD1 Signaling Is Required for Cardiac Ventricular Compaction.. JCI insight 4 (16) : e125908. ScholarBank@NUS Repository. https://doi.org/10.1172/jci.insight.125908
Abstract: Left ventricular noncompaction (LVNC) is one of the most common forms of genetic cardiomyopathy characterized by excessive trabeculation and impaired myocardial compaction during fetal development. Patients with LVNC are at higher risk of developing left/right ventricular failure or both. Although the key regulators for cardiac chamber development are well studied, the role of semaphorin (Sema)/plexin signaling in this process remains poorly understood. In this article, we demonstrate that genetic deletion of Plxnd1, a class-3 Sema receptor in endothelial cells, leads to severe cardiac chamber defects. They were characterized by excessive trabeculation and noncompaction similar to patients with LVNC. Loss of Plxnd1 results in decreased expression of extracellular matrix proteolytic genes, leading to excessive deposition of cardiac jelly. We demonstrate that Plxnd1 deficiency is associated with an increase in Notch1 expression and its downstream target genes. In addition, inhibition of the Notch signaling pathway partially rescues the excessive trabeculation and noncompaction phenotype present in Plxnd1 mutants. Furthermore, we demonstrate that Semaphorin 3E (Sema3E), one of PlexinD1’s known ligands, is expressed in the developing heart and is required for myocardial compaction. Collectively, our study uncovers what we believe to be a previously undescribed role of the Sema3E/PlexinD1 signaling pathway in myocardial trabeculation and the compaction process.
Source Title: JCI insight
URI: https://scholarbank.nus.edu.sg/handle/10635/168452
ISSN: 23793708
DOI: 10.1172/jci.insight.125908
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