Calcium at Fertilization and in Early Development

Abstract

Fertilization calcium waves are introduced, and the evidence from which we can infer general mechanisms of these waves is presented. The two main classes of hypotheses put forward to explain the generation of the fertilization calcium wave are set out, and it is concluded that initiation of the fertilization calcium wave can be most generally explained in invertebrates by a mechanism in which an activating substance enters the egg from the sperm on sperm-egg fusion, activating the egg by stimulating phospholipase C activation through a src family kinase pathway and in mammals by the diffusion of a sperm-specific phospholipase C from sperm to egg on sperm-egg fusion. The fertilization calcium wave is then set into the context of cell cycle control, and the mechanism of repetitive calcium spiking in mammalian eggs is investigated. Evidence that calcium signals control cell division in early embryos is reviewed, and it is concluded that calcium signals are essential at all three stages of cell division in early embryos. Evidence that phosphoinositide signaling pathways control the resumption of meiosis during oocyte maturation is considered. It is concluded on balance that the evidence points to a need for phosphoinositide/calcium signaling during resumption of meiosis. Changes to the calcium signaling machinery occur during meiosis to enable the production of a calcium wave in the mature oocyte when it is fertilized; evidence that the shape and structure of the endoplasmic reticulum alters dynamically during maturation and after fertilization is reviewed, and the link between ER dynamics and the cytoskeleton is discussed. There is evidence that calcium signaling plays a key part in the development of patterning in early embryos. Morphogenesis in ascidian, frog, and zebrafish embryos is briefly described to provide the developmental context in which calcium signals act. Intracellular calcium waves that may play a role in axis formation in ascidian are discussed. Evidence that the Wingless/calcium signaling pathway is a strong ventralizing signal in Xenopus, mediated by phosphoinositide signaling, is adumbrated. The central role that calcium channels play in morphogenetic movements during gastrulation and in ectodermal and mesodermal gene expression during late gastrulation is demonstrated. Experiments in zebrafish provide a strong indication that calcium signals are essential for pattern formation and organogenesis.

Ca2+ signaling differentiation during oocyte maturation

“…embryonic mitotic cell cycle. Both of these critical events are dependent on the specialized Ca 2þ transient at fertilization (Stricker, 1999;Runft et al, 2002;Whitaker, 2006).…”

Fertilization and Nicotinic Acid Adenine Dinucleotide Phosphate Induce pH Changes in Acidic Ca2+ Stores in Sea Urchin Eggs

“…The mechanism of activation of the egg upon fertilization encompasses the rapid increases in the cytosolic pH and intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) important for fertilization envelope formation, DNA and protein synthesis, and embryological development (2). The pattern of [Ca 2ϩ ] i changes within the egg are highly organized spatio-temporally and reflect the precisely timed and placed recruitment of different families of Ca 2ϩ channels resident upon either the plasma membrane or intracellular organelles (2,3). After the initial transient "cortical flash" caused by Ca 2ϩ influx across the plasma membrane (2-5), Ca 2ϩ release from intracellular stores is manifest as a Ca 2ϩ wave that propagates across the entire egg initiating from the point of sperm entry (2).…”

“…The pattern of [Ca 2ϩ ] i changes within the egg are highly organized spatio-temporally and reflect the precisely timed and placed recruitment of different families of Ca 2ϩ channels resident upon either the plasma membrane or intracellular organelles (2,3). After the initial transient "cortical flash" caused by Ca 2ϩ influx across the plasma membrane (2-5), Ca 2ϩ release from intracellular stores is manifest as a Ca 2ϩ wave that propagates across the entire egg initiating from the point of sperm entry (2). These phasic elevations in [Ca 2ϩ ] i are driven by a complex interplay between the second messengers inositol 1,4,5-trisphosphate, cyclic adenosine diphosphoribose, and nicotinic acid adenine dinucleotide phosphate (NAADP) 2 (1).…”

“…After the initial transient "cortical flash" caused by Ca 2ϩ influx across the plasma membrane (2-5), Ca 2ϩ release from intracellular stores is manifest as a Ca 2ϩ wave that propagates across the entire egg initiating from the point of sperm entry (2). These phasic elevations in [Ca 2ϩ ] i are driven by a complex interplay between the second messengers inositol 1,4,5-trisphosphate, cyclic adenosine diphosphoribose, and nicotinic acid adenine dinucleotide phosphate (NAADP) 2 (1). Importantly, the relative contribution of each messenger to each phase of the Ca 2ϩ signal is different, e.g.…”

Expression and reconstitution of the bioluminescent Ca2+ reporter aequorin in human embryonic stem cells, and exploration of the presence of functional IP3 and ryanodine receptors during the early stages of their differentiation into cardiomyocytes

“…It has long been known that Ca 2+ signaling plays a key role in many aspects of embryonic development (Jaffe, 1999;Berridge et al, 2000;Webb and Miller, 2003;Whitaker, 2006Rosenberg and Spitzer, 2011), as well as controlling a wide variety of cellular functions (Szent-Györgyi, 1975;Berridge, 1993;Peterson et al, 1994;Bootman and Lipp, 2001;West et al, 2001). Indeed, well-defined Ca 2+ signals have been demonstrated to correlate with, and sometimes to directly initiate and/or regulate, distinct morphological events (Homa et al, 1993;Swann et al, 1994;Chang and Meng, 1995;Webb et al, 1997;Leung et al, 1998;Créton et al, 2000;Porter et al, 2003;Ma et al, 2009;Lohmann, 2009;Cheung et al, 2011).…”