Fertilization leads to the formation of zygote. The process of segmentation (fractionation) immediately follows fertilization or another process that activates the egg. Cleavage consists of the division of the zygote into a large number of cell units. The cells that form during segmentation are called blastomeres. Cleavage model of mouse embryos during the transition from 2 to 4 cells. The bicellular blastomeres of mice divide either southern (M) or equatorial (E), creating four types of embryos: ME, EM, MM and EE. Depending on the crack plane, blastomere offspring colonize different regions of the blastocyst (see main text for details). In addition, embryos that have undergone at least one meridian division (ME, ME and MM) develop significantly more efficiently than EE embryos (data from Piotrowska-Nitsche and Zernicka-Goetz, 2005). A, animal bar; V, vegetal pole. Despite this diversity of cleavages, the molecular mechanisms that regulate early embryonic divisions remain strongly preserved in strains. Interactions between polarity indices, cytoskeleton and cell-to-cell communication are essential for cleavage in a variety of species studied, from Caenorhabditis elegans to mice.
In this work, we would like to introduce these universal mechanisms that guide embryos together through cleavage and discuss their possible meaning as quality biomarkers of human embryos. The processes of karyokinesia (mitosis) and cytokinesis work together to lead to cleavage. The mitotic apparatus consists of a central pin and polar asters made of polymers of the tubulin protein called microtubules. Asters are nucleated by centrosomes and centrosomes are organized by centrioles, which are introduced into the egg by sperm as basal bodies. Cytokinesis is mediated by the contractile ring, which consists of polymers of the actin protein called microfilaments. Karyokinesis and cytokinesis are independent but spatially and temporally coordinated processes. While mitosis can occur in the absence of cytokinesis, cytokinesis requires the mitotic apparatus. The transition from fertilization to cleavage is caused by the activation of mitosis promoting factor (MPF).
MPF was first discovered as the main factor responsible for the resumption of meiotic cell division in the ovulated frog. It continues to play a role after fertilization, regulating the biphasic cell cycle of early blastomeres. Blastomeres typically undergo a cell cycle consisting of only two steps: M (mitosis) and S (DNA synthesis) (Figure 8.2). Gerhart et al. (1984) showed that MPF undergoes cyclical changes in its activity level in mitotic cells. MPF activity in early blastomeres is highest during M and undetectable during S. Newport and Kirschner (1984) showed that DNA replication (S) and mitosis (M) are solely motivated by gain and loss of MPF activity. Cission cells can be trapped experimentally in the S phase by being incubated in a protein synthesis inhibitor. When MPF is microinjected into these cells, they enter M. Their nuclear envelope collapses and their chromatin condenses into chromosomes. After one hour, the MPF is degraded and the chromosomes return to the S phase.
The establishment of cell polarity is one of the most important events during early embryonic divisions. In most species, including mammals, it allows cells to assume different developmental destinies. The main signaling pathway for cell polarization, mediated by defective partitioning proteins (PARs), was discovered in C. elegans embryos because it can influence the asymmetry of the first cleavage division (Kemphues et al., 1988). Prior to fertilization, PAR-3, PAR-6 and PKC-3 (the nematode homologue of PKCa) are present throughout eichortex and PAR-1 and PAR-2 are located in the cytoplasm (Munro and Bowerman, 2009; Nance and Zallen, 2011). After fertilization, the PAR and PKC-3 proteins are polarized, with PAR-1 and 2 in the cortex above the sperm-derived centrosome (marking it as the posterior pole) (Guo and Kemphues, 1995; Boyd et al., 1996) and PAR-3, PAR-6 and PKC-3 in the cortex of the opposite anterior pole (Fig. 1A) (Etemad-Moghadam et al., 1995; Tabuse et al., 1998; Hung and Kemphues, 1999). PAR-4 and PAR-5, on the other hand, are uniformly localized throughout the cortex of the 1-cell embryo (Watts et al., 2000; Morton et al., 2002).
