Cell cycle control in the early embryonic development of aquatic animal species

Abstract

The cell cycle is integrated with many aspects of embryonic development. Not only is proper control over the pace of cell proliferation important, but also the timing of cell cycle progression is coordinated with transcription, cell migration, and cell differentiation. Due to the ease with which the embryos of aquatic organisms can be observed and manipulated, they have been a popular choice for embryologists throughout history. In the cell cycle field, aquatic organisms have been extremely important because they have played a major role in the discovery and analysis of key regulators of the cell cycle. In particular, the frog Xenopus laevis has been instrumental for understanding how the basic embryonic cell cycle is regulated. More recently, the zebrafish has been used to understand how the cell cycle is remodeled during vertebrate development and how it is regulated during morphogenesis. This review describes how some of the unique strengths of aquatic species have been leveraged for cell cycle research and suggests how species such as Xenopus and zebrafish will continue to reveal the roles of the cell cycle in human biology and disease.

DNA replication timing during development anticipates transcriptional programs and parallels enhancer activation

“…We collected cells from pre-MBT zebrafish embryos (2.75 hpf), which are almost entirely in S-phase (Siefert et al 2015), and compared them to the 28 hpf G1 reference as described above to assess replication timing. Considering that the genome (1.4 Gb) is replicated in <15 min during the pre-MBT cell cycles and pre-MBT embryos lack a G1-phase, we anticipated that the timing program would be random and unstructured (Siefert et al 2015). To demonstrate the difference in temporal resolution, we scaled the replication timing data to the length of S-phase and plotted the temporal order based on actual time in S-phase.…”

“…In the early stages of development, cells are highly proliferative and primarily in S-phase (Supplemental Fig. S6; Siefert et al 2015); therefore, the early embryos were processed as S-phase samples and compared to the G1 reference as described above. Genome-wide changes in replication timing throughout development were assessed by comparing replication timing values at each developmental stage in a Pearson's correlation matrix (Fig.…”

“…The zebrafish is also a powerful model to study how the embryonic cell cycle is remodeled, when cells undergo numerous profound transcriptional, epigenetic, and structural changes necessary for normal development (Newport and Kirschner 1982;Farrell and O'Farrell 2014;Siefert et al 2015). Prior to the midblastula transition (MBT), the embryonic cells undergo 10 rapid cell cycles consisting only of S/M phases, and the entire genome (1.4 Gb) is replicated in <15 min (Kane and Kimmel 1993;Vastenhouw et al 2010;Siefert et al 2015). Pre-MBT embryos lack a G1-phase, which is thought to be necessary for the establishment of the replication timing program (Dimitrova and Gilbert 1999;Lu et al 2010).…”

“…After the MBT, widespread transcription begins, and certain histone modifications associated with transcriptional activation and repression are added (Vastenhouw et al 2010). Cell cycle remodeling also commences at the MBT, with initial S-phase lengthening and the appearance of a G2-phase (Siefert et al 2015). Furthermore, zebrafish display a conserved fate map after the blastula stage, and like other vertebrates, undergo cell fate restrictions to form germ layers during gastrulation (Kimmel et al 1990).…”

Increasing demand for plasma membrane contributes to the energetic cost of early zebrafish embryogenesis

“…Interestingly, the increase in heat dissipation slows down after cleavage and again after gastrulation during frog development (Nagano & Ode, 2014). These slow-downs coincide with the embryos mid-blastula transition and gastrulation during which the embryonic cell cycle lengthens by about 3fold and 8-fold respectively (Ferree, 2016;Siefert, 2015). A longer cell cycle time and, thus, a slower increase in surface area, could account for this observed slow-down.…”