Impairment of endothelial‐mesenchymal transformation during atrioventricular cushion formation in Tmem100 null embryos. Issue 1 (7th November 2014)

• Record Type: Journal Article
• Authors: Mizuta, Ken; Sakabe, Masahide; Hashimoto, Aya; Ioka, Tomoko; Sakai, Chihiro; Okumura, Kazuki; Hattammaru, Miwa; Fujita, Masahide; Araki, Mutsumi; Somekawa, Satoshi; Saito, Yoshihiko; Nakagawa, Osamu
• Is Part Of: Developmental dynamics. Volume 244:Issue 1(2015:Jan.)
• Page Start: 31
• Page End: 42
• Publication Date: 2014-11-07
• Subjects: Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.24216
• Languages: English
• ISSNs: 1058-8388

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <underline>Background:</underline> Endothelial‐mesenchymal transformation (EndMT) is essential for endocardial cushion formation during cardiac morphogenesis. We recently identified <italic>Tmem100</italic> as an endothelial gene indispensable for vascular development. In this study, we further investigated its roles for EndMT during atrioventricular canal (AVC) cushion formation. <underline>Results:</underline><italic>Tmem100</italic> was expressed in AVC endocardial cells, and <italic>Tmem100</italic> null embryos showed severe EndMT defect in the AVC cushions. While calcineurin‐dependent suppression of vascular endothelial growth factor (VEGF) expression in the AVC myocardium is important for EndMT, significant up‐regulation of <italic>Vegfa</italic> expression was observed in <italic>Tmem100</italic> null heart. EndMT impaired in <italic>Tmem100</italic> null AVC explants was partially but significantly restored by the expression of constitutively‐active calcineurin A, suggesting dysregulation of myocardial calcineurin‐VEGF signaling in <italic>Tmem100</italic> null heart. Moreover, <italic>Tmem100</italic> null endocardial cells in explant culture did not show EndMT in response to the treatment with myocardium‐derived growth factors, transforming growth factor β2 and bone morphogenetic protein 2, indicating involvement of an additional endocardial‐specific abnormality in the mechanism of EndMT defect. The lack of NFATc1 nuclear translocation in endocardial cells of <italic>Tmem100</italic> null embryos suggests impairment of endocardial calcium signaling. <underline>Conclusions:</underline> The <italic>Tmem100</italic> deficiency causes EndMT defect during AVC cushion formation possibly via disturbance of multiple calcium‐related signaling events. <italic>Developmental Dynamics 244:31–42, 2015</italic>. © 2014 Wiley Periodicals, Inc.</p> </abstract>