Calcium Signaling in Vertebrate Development and Its Role in Disease

Abstract

Accumulating evidence over the past three decades suggests that altered calcium signaling during development may be a major driving force for adult pathophysiological events. Well over a hundred human genes encode proteins that are specifically dedicated to calcium homeostasis and calcium signaling, and the majority of these are expressed during embryonic development. Recent advances in molecular techniques have identified impaired calcium signaling during development due to either mutations or dysregulation of these proteins. This impaired signaling has been implicated in various human diseases ranging from cardiac malformations to epilepsy. Although the molecular basis of these and other diseases have been well studied in adult systems, the potential developmental origins of such diseases are less well characterized. In this review, we will discuss the recent evidence that examines different patterns of calcium activity during early development, as well as potential medical conditions associated with its dysregulation. Studies performed using various model organisms, including zebrafish, Xenopus, and mouse, have underscored the critical role of calcium activity in infertility, abortive pregnancy, developmental defects, and a range of diseases which manifest later in life. Understanding the underlying mechanisms by which calcium regulates these diverse developmental processes remains a challenge; however, this knowledge will potentially enable calcium signaling to be used as a therapeutic target in regenerative and personalized medicine.

Keywords: Xenopus; animal model; calcium; development; embryo; human disease; mouse; zebrafish.

Figure 1

Comparative calcium activity among zebrafish, frogs, and mice during egg activation and fertilization (A), first cleavage (Ba), second cleavage (Bb), blastula (C), gastrulation and neural induction (D) and organogenesis (E), including neural tube closure (Ea) and muscle development (Eb) in zebrafish, Xenopus, and mouse; also, depiction of calcium dynamics immediately after tissue damage (Fa) and calcium mediated actomyosin filament (green lining) during wound healing and regeneration (Fb). Black arrows show direction of propagation of calcium waves. Y, yolk; A, anterior; P, posterior; D, dorsal; V, ventral; BP, blastopore; NP, neural plate; UPM, unsegmented paraxial mesoderm; MS, matured somites; SS, segmenting somites; IS, injury site; N, nucleus. Images were adapted and re-drawn from [136,137,138].