Vertebrate Development Maternal to Zygotic Control (Advances in Experimental Medicine and Biology)

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Cdk1-stimulating and mitosis- promoting effect. Intriguingly, Xenopus egg extract studies
revealed that PP1 is crucial for the execution of mitotic exit (Wu et al. 2009 ). PP1 would
be an excellent candidate for a mitotic kinase-counteracting phosphatase, because it was
shown that the activity of the catalytic PP1 subunit is decreased through direct phosphory-
lation by Cdk1 (Dohadwala et al. 1994 ) and inhibitory phosphorylation of PP1 appears in
prophase of mitosis and peaks in metaphase, closely resembling the activity pattern of
Cdk1/cyclin-B (Kwon et al. 1997 ). After inactivation of MPF by degradation of cyclin-B,
PP1 likely activates itself by autodephosphorylation (Wu et al. 2009 ). This mechanism
ensures that the activities of PP1 and Cdk1/cyclin-B occur in a mutually exclusive manner.
The extent to which PP1 directly contributes to the dephosphorylation of mitotic phospho-
proteins is still under debate and may also vary between organisms. Data from mammalian
and Drosophila tissue culture cells indicate that PP1 is directly involved in the deconden-
sation of the chromatin and nuclear envelope reassembly during mitotic exit (Steen et al.
2000 ; Afonso et al. 2014 ; Thompson et al. 1997 ). Studies in fission yeast revealed that PP1
is at the top of a cascade that reactivates mitotically inactivated PP2A-B55 and PP2A-B ́56
holoenzymes after the metaphase-to-anaphase transition (Grallert et al. 2015 ). Thus, PP1
seems to have multiple functions during mitotic exit including the function of an ‘initiator’
(i.e. activation of other phosphatases) as well as ‘executing’ (i.e. dephosphorylation of
mitotic proteins) phosphatase.


3.7 Basic Plan of the Cell Cycle in Early Development


The development of multicellular organisms begins with a single fertilised egg, the
zygote. This zygote undergoes cleavage, which involves multiple rounds of extremely
rapid cell division cycles during which the volume of the zygote remains the same but
the cell number increases. These cells are called blastomeres. As they divide, they orga-
nise into a hollow ball of cells, the blastula. During gastrulation the blastula undergoes
dramatic cell movements, followed by cell-fate specification ultimately giving rise to the
adult organism. In mammals, the blastula is referred to as a blastocyst whose implanta-
tion into the uterus is a crucial step during development. Obviously, the formation of an
organism is a challenging process and different organisms employ different strategies to
ensure success of the reproductive process. Some vertebrates such as amphibians and
most fish follow the strategy of external fertilisation and therefore lay numerous eggs to
increase the chances of having a few viable progeny since they are not protected by the
parents. Reproduction in mammals, on the other hand, typically involves internal fertili-
sation and viviparity, i.e. the development of the embryo inside of the female, which
results in the birth of only a few offspring. Therefore, cell division mechanisms could
have undergone selective evolution to match the requirements of different species.
Xenopus eggs, once fertilised, undergo one ‘long’ first cell cycle followed by eleven
rapid and synchronous divisions (2–12) to generate blastulae, which contain about 4000
cells (Newport and Kirschner 1984 ). These rapid divisions lack not only gap phases but
also checkpoints such as the SAC and DNA damage checkpoint. In addition, transcrip-
tion from zygotic chromatin is blocked because of its highly compacted, H3-methylated
and hypo-acetylated nature, and all translation events occur from maternal mRNAs


A. Heim et al.

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