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M-phase in mice, a characteristic which might account for the prolonged M-phase
(Kubiak and Ciemerych 2001 ).
In Xenopus, the mechanism resulting in an elongated first division seems to be dis-
tinct to the one in mice, and one of its most important features is the presence of inhibi-
tory phosphorylations of Cdk1 at T14 and Y15. As aforementioned, the basic feature
of these phosphorylations is that they keep Cdk1 inhibited in spite of increasing levels
of cyclin-B. The kinases mediating these inhibitory phosphorylations, Wee1 and Myt1,
are usually counteracted by the phosphatase Cdc25. But, during the first cell cycle in
Xenopus, this antagonism via Cdc25 seems to be kept at a minimum due to the action
of the proto-oncogenic protein kinase c-Mos, which is active at this stage and triggers
the activation of the MEK/MAP kinase (MAPK) signalling cascade (Murakami and
Vande Woude 1998 ). c-Mos is a serine/threonine kinase which was originally identi-
fied as the transforming gene of Moloney murine sarcoma virus, causing cellular trans-
formation (Oskarsson et al. 1980 ). Expression of c-Mos was found to be tissue-specific,
e.g. in mice (Paules et al. 1989 ) and frogs (Sagata et al. 1988 ), high concentrations of
c-Mos transcripts were found in the oocytes in contrast to very low concentrations in
the brain and testes. The c-Mos/MEK/MAPK pathway has been reported to have an
activating function on Wee1 (Murakami and Vande Woude 1998 ; Murakami et al.
1999 ; Walter et al. 2000 ), and strong MAPK activation can negatively affect Cdc25A
function by phosphorylating Cdc25A and thereby targeting it for destruction via the
SCFβ-TRCP E3 ligase (Fig. 3.4) (Isoda et al. 2009 ). Accordingly, inhibition of the MAPK
cascade by a small molecule inhibitor against MEK (U0126) results in decreased Cdk1
Y15 phosphorylation levels and shortened length of the first cell cycle, proving the
importance of the c-Mos/MEK/MAPK cascade in ensuring proper length of the first
cell cycle (Tsai et al. 2014 ). Following fertilisation, c-Mos undergoes selective protein
destruction. The destruction of c-Mos within approximately 20–30 min after fertilisa-
tion depends on its N-terminal proline residue (Nishizawa et al. 1993 ). This N-terminal
proline was shown to affect the net phosphorylation of serine-2, a modification which
slows down c-Mos degradation in oocytes (Nishizawa et al. 1992 ; Sheng et al. 2002 ).
As the first cell cycle progresses, the levels of c-Mos decline, resulting in a lowering of
its ability to antagonise Cdk1/cyclin-B activation. The balance is further tipped by the
action of Xenopus Polo-like-kinase1 (Plx1), which promotes Cdk1/cyclin-B activation
by two mechanisms: first, by activating Cdc25 (Abrieu et al. 1998 ; Qian et al. 1998 ;
Toyoshima-Morimoto et al. 2002 ), and second, specifically during embryonic M-phase,
by inhibiting Myt1 (Inoue and Sagata 2005 ).
3.7.2 The Early Embryonic Cell Cycles
After the prolonged first cell cycle, embryos enter a series of specialised rapid early
embryonic division cycles. In Xenopus, these rapid division cycles are highly syn-
chronous and result in formation of the blastula (Newport and Kirschner 1982 , 1984 ).
The length of early embryonic divisions varies drastically between species, from
15 min in Zebrafish, 30 min in Xenopus, to around 12 h in mice (Artus and Cohen-
Tannoudji 2008 ). The early divisions in mammalian embryos are characterised not
A. Heim et al.