Mechanisms involved in valvuloseptal endocardial cushion formation in early cardiogenesis: Roles of transforming growth factor (TGF)‐β and bone morphogenetic …

Y Nakajima, T Yamagishi, S Hokari… - … Record: An Official …, 2000 - Wiley Online Library
Y Nakajima, T Yamagishi, S Hokari, H Nakamura
The Anatomical Record: An Official Publication of the American …, 2000Wiley Online Library
Endothelial‐mesenchymal transformation (EMT) is a critical event in the generation of the
endocardial cushion, the primordia of the valves and septa of the adult heart. This embryonic
phenomenon occurs in the outflow tract (OT) and atrioventricular (AV) canal of the
embryonic heart in a spatiotemporally restricted manner, and is initiated by putative
myocardially derived inductive signals (adherons) which are transferred to the endocardium
across the cardiac jelly. Abnormal development of endocardial cushion tissue is linked to …
Abstract
Endothelial‐mesenchymal transformation (EMT) is a critical event in the generation of the endocardial cushion, the primordia of the valves and septa of the adult heart. This embryonic phenomenon occurs in the outflow tract (OT) and atrioventricular (AV) canal of the embryonic heart in a spatiotemporally restricted manner, and is initiated by putative myocardially derived inductive signals (adherons) which are transferred to the endocardium across the cardiac jelly. Abnormal development of endocardial cushion tissue is linked to many congenital heart diseases. At the onset of EMT in chick cardiogenesis, transforming growth factor (TGFβ)‐3 is expressed in transforming endothelial and invading mesenchymal cells, while bone morphogenetic protein (BMP)‐2 is expressed in the subjacent myocardium. Three‐dimensional collagen gel culture experiments of the AV endocardium show that 1) myocardially derived inductive signals upregulate the expression of AV endothelial TGFβ3 at the onset of EMT, 2) TGFβ3 needs to be expressed by these endothelial cells to trigger the initial phenotypic changes of EMT, and 3) myocardial BMP2 acts synergistically with TGFβ3 in the initiation of EMT. Anat Rec 258:119–127, 2000. © 2000 Wiley‐Liss, Inc.
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