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Many metazoans, including nonmammalian vertebrates, undergo a cleavage
stage, though cell cycle timing varies (Table 9.1). In zebrafish embryos, the first cell
division is initiated approximately 45 min after fertilization, followed by nine cell
cycles, each lasting ~15 min. After ten cleavage divisions, embryos initiate the
MBT and cell cycle remodeling commences (Kane and Kimmel 1993 ). Amphibian
embryonic cycles have similar dynamics though cleavage cycles are longer. In
Xenopus laevis, the first cleavage occurs ~90 min after fertilization and is followed
by 11 additional ~25 min cleavage cycles before the MBT is triggered (Newport and
Kirschner 1982a; Wu and Gerhart 1980 ). In contrast, mammals delay first cleavage,
with mice undergoing the first cell division 12 h after fertilization. Mammalian
embryos then enter a period of slower, asynchronous cell divisions to reach the
morula stage and do not typically undergo a phase analogous to the rapid cleavage
divisions seen in nonmammalian vertebrates.
9.2.2 Molecular Basis of Rapid Cleavages
Cleavage cycles employ many of the same regulators found in somatic cell cycles
(for an in-depth description of cell cycle regulation in somatic cells and the early
embryo, please see Chapter 3 ). However, early embryos have adapted their func-
tions significantly in order to drive rapid cell proliferation, particularly the regula-
tion of Cyclin-dependent kinase (Cdk) activity. The following section describes the
specialized Cdk regulation in cleavage cycles, including cyclin availability, synthe-
sis and proteolysis, and Cdk phosphorylation.
Cdks are a family of highly conserved serine–threonine kinases that regulate cell
cycle transitions by targeting hundreds of substrates to promote cell cycle progres-
sion (Ubersax et al. 2003 ). While Cdk protein levels remain relatively constant for
the duration of the cell cycle, Cdk activity is highly oscillatory and relies on several
independent mechanisms to ensure stringent control. Cdk activity depends on both
Table 9.1 Zygotic gene activation and MBT in vertebrate embryos
OrganismDuration of cleavage
divisionsa# divisions to
earliest ZGAb# divisions to
MBTcTime to
large-scale ZGA
Xenopus 20–25 min 6 12 6–7 h
Zebrafish 15 min 6 10 3.5 h
Medaka 35 min 6 11–12 7–8 h
Mouse <12 h 0–1 – 24 h
Human <12 h 2 – 24–48 h
Chickd – 6–7 – –
aNot including the first cell division, which is longer than subsequent cleavage divisions
bZGA: zygotic gene activation
cMBT: midblastula transition, a discrete transition associated with the co-appearance of asynchro-
nous divisions, cell cycle checkpoints, and large-scale zygotic gene activation
dChick divisions are asynchronous after the fourth division (Lee et al. 2013a)
M. Zhang et al.