101stockpiled into the giant oocyte (Akkers et al. 2009 ; Hontelez et al. 2015 ; Thompson
et al. 1998 ). The time when active transcription begins in the zygotic genome (zygotic
genome activation, ZGA) varies heavily between different organisms. In Xenopus
embryos, ZGA and midblastula transition (MBT)—a major developmental transition
involving activation of cell motility leading to gastrulation—begin at about the same
time at the 13th cycle (Kimelman et al. 1987 ) (see Chap. 9 ). Zebrafish embryos also
undergo 13 cycles until MBT, but ZGA occurs during the course of the tenth cycle
(Tadros and Lipshitz 2009 ; Kane and Kimmel 1993 ). In contrast, in mice, ZGA occurs
at the two-cell stage (Bolton at al. 1984 ; Thompson et al. 1998 ), and it requires three
more divisions until embryonic cells undergo compaction, i.e. they activate cell-cell
adhesion and form the 16-celled morula, which ultimately differentiates into the blasto-
cyst containing the inner cell mass (ICM) and trophoblast (Thompson et al. 1998 ). This
blastocyst is implanted on the uterine wall and undergoes gastrulation to give rise to the
gastrula. Like any type of cell cycle, early embryonic divisions are driven, primarily, by
accumulation and destruction of cyclin-B albeit with modulations that enable the special
features of the first cell cycle as compared to the following cleavage cycles, which are
rapid and synchronous in organisms such as Xenopus and most fish and asynchronous
in mammals.
3.7.1 The First Mitotic Cell Division
The first mitotic cell cycle in a vertebrate zygote begins with the completion of
meiosis II and extrusion of the second polar body. In addition, sperm chromatin
has to be incorporated into the egg to allow pronuclear fusion and embryonic
development. This is initiated by the breakdown of its nuclear envelope followed
by decondensation of chromatin and replacement of sperm protamine by somatic
histones (Rodman et al. 1981 ; MacLay and Clarke 2003). Subsequently, the sperm
chromatin recondenses to form the male pronucleus (Kubiak and Ciemerych
2001 ). The de novo assembly of nucleosomes composed of the canonical histone
proteins is an important step to enable the paternal genome to contribute to the
formation of the diploid zygote. Following the reassembly of the nuclear enve-
lope, DNA replication initiates (McLay and Clarke 2003 ). In some vertebrates
such as mice, DNA replication and the mitotic cell cycle ensue before the male
and female pronuclei fuse (Ciemerych and Czolowska 1993 ; Mayer et al. 2000 ),
while in others such as Zebrafish and Xenopus, the maternal and paternal pronu-
clei fuse before they undergo mitosis (Ubbels et al. 1983 ; Dekens et al. 2003 ).
Thus, the first mitotic division has a work programme that is clearly distinct from
any other cell division. This characteristic is reflected in the length of the first
division. In Xenopus, the first cell cycle takes about three times as long as the fol-
lowing fast 30-min cycles (Newport and Kirschner 1982 ). In mice, the total
lengths of the first and second cell cycles are comparable (19–20 h), but the first
mitotic M-phase cycle lasts for about 120 min as compared to 70 min in the sec-
ond division (Artus and Cohen-Tannoudji 2008 ; Ciemerych et al. 1999 ; Sikora-
Polaszek et al. 2006 ). Reportedly, cyclin-A2 remains stable during the first
3 Regulation of Cell Division