Notch signalling in cardiovasculogenesis: insight into their role in early cardiovascular development
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Notch signalling in cardiovasculogenesis: insight into their role in early cardiovascular development Marimuthu Saravanakumar • Halagowder Devaraj
Received: 24 August 2012 / Accepted: 18 December 2012 / Published online: 27 December 2012 Ó Springer Science+Business Media Dordrecht 2012
Abstract The role of Notch signalling in congenital cardiovascular disease is evident by the identification of human mutations in several Notch signalling components, which also indicates the importance of activated Notch pathway in cardiovascular biology. Therefore, the aim of the present study is to investigate the expression pattern of the components of Notch signalling molecules and their role in mice embryonic heart and vascular development. Group A: normal control pregnant mice, group B: pregnant mice were injected with DMSO, group C: DAPT were subcutaneously injected to pregnant mice. The morphological and molecular changes of trabeculation-defective phenotype were analysed using histological, scanning electron microscope, immunoblot, immunolocalization and reverse transcriptasePCR. E15.5 DAPT-treated mice revealed that there was a major reduction in the formation of septal walls between the ventricular chambers compared with normal control pregnant mice. VEGF expression was found in the DAPT treated and wild-type embryonic artery, whereas notch target genes GATA4, Hey1 expression were not found in the DAPT treated mice embryo. The role of Notch in ventricular development is supported by the trabeculation-defective phenotype seen in standard and endocardial-specific inhibition of Notch targets. The present study reveals the significant role of Notch signalling during the formation of ventricular septum and proper development of endothelial cell lineage and its precursor in mice cardiogenesis.
M. Saravanakumar H. Devaraj (&) Unit of Biochemistry, Department of Zoology, University of Madras, School of Life Sciences, Maraimalai Campus, Guindy, Chennai 600 025, Tamil Nadu, India e-mail: [email protected]
Keywords CVD VEGF Tbx2 DAPT Notch signalling
Introduction Congenital heart disease (CHD) represents the most common type of human birth defect and the most common noninfectious cause of death in children. It was found that the incidence of CHD range from 1 to 5 % of human live births [1]. The morphologic features of CHD have been carefully described and categorized based on the specific regions of the heart that are affected. It has been observed that infants born with CHD typically have isolated cardiovascular defects affecting only one chamber, either septum or valve of the heart. These findings suggest that relatively independent molecular developmental programs might exist for each specific region of the heart [2]. The role of Notch signalling in congenital cardiovascular disease is evident by the identification of human mutations in several Notch signalling components, which also indicates the importance of activated Notch pathway in cardiovascular biology [3–5]. In mouse models, targeted disruption of many genes
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