Programmed cell death in the developing heart.

Abstract

In humans every minute millions of cells die by programmed cell death and by the end of their life almost 99.9% of all cells once made have undergone this fate [1]. The functionality of cell death is different during development and adult life. During development apoptosis serves three major functions: deleting vestigial structures, i.e. phylogenetic cell death; controlling cell numbers, i.e. histogenetic cell death, and remodeling structures, i.e. morphogenetic cell death [2]. In adult life, apoptosis mainly serves to maintain homeostasis by counterbalancing mitosis and deleting cells, which are potentially autoimmunoreactive, malignant, or virus infected [3,4]. In contrast to adult life cell death, where cell death is generally considered a pathological event, during cardiac development cell death is a physiological event that is highly regulated in space and time. It took till 1968 when cell death was first recognized in the chicken ventricular myocardium [5]. In the next decade, the spatiotemporal pattern of cell death in the developing heart was extensively studied, in particular by the groups of Pexieder [6–10], Okamoto [11–14] and Ojeda [15–18]. These studies accurately described cell death patterns, but the underlying mechanisms and functions were not addressed. Despite the large body of data regarding the spatiotemporal patterns of cell death in the developing heart, a comprehensive overview of cell death in this developing organ is difficult to obtain. This is mainly because the original data were not published in regular journals and/or in the German language. Moreover, the nomenclature of the various structures of the developing heart has changed significantly during the last decades, which adds to the imperviousness of the data. The objective of this review is to bring together data derived from the earlier as well as from recent studies, and to generate a map of cardiac cell … * Corresponding author. Tel.: +31-20-5669-111; fax: +31-20-6976-177 m.j.vandenhoff{at}amc.uva.nl a.f.moorman{at}amc.uva.nl