154
and α-/β-catenin are expressed in mouse embryos as early as the zygote stage, it is
unclear how the process of compaction is initiated (Vestweber et al. 1987 ; Ohsugi
et al. 1996 ). Of note, compaction still occurs even if transcription is inhibited begin-
ning at the four-cell stage (Kidder and McLachlin 1985 ) and in fact can be prema-
turely induced by incubating four-cell embryos with protein synthesis inhibitors
(Levy et al. 1986 ). This suggests that all the components required for embryo com-
paction have been synthesized by the four-cell stage, and, given that premature
compaction is observed in the presence of protein kinase activation as well, it also
indicates that compaction is under the control of posttranslational regulation via
phosphorylation (reviewed in Cockburn and Rossant 2010 ). Indeed, both E-cadherin
and β-catenin become phosphorylated at the time of compaction (Pauken and Capco
1999 ), and a recent report demonstrated that E-cadherin-dependent filopodia are
responsible for the cell shape changes necessary for compaction in mouse embryos
(Fierro-González et al. 2013 ). Using live-cell imaging and laser ablation, this study
determined that filopodia extension is tightly coordinated with blastomere elonga-
tion and that the inhibition of filopodia components, E-cadherin, α-/β-catenin,
F-actin, and myosin-X, prevented cellular elongation and mouse embryo compac-
tion. Whether other mammalian embryos establish and/or maintain cell elongation
by similarly extending filopodia is not known, but an earlier time for the initiation
of compaction correlates with implantation success in human IVF embryos (Landry
et al. 2006 ; Skiadas et al. 2006 ).
Along with cell elongation, intracellular polarization also occurs during compac-
tion, whereby the outward-facing, or apical, region of each blastomere becomes
distinct from the inward-facing (basolateral) regions at least in mouse embryos. In
particular, the blastomere nuclei move basolaterally, whereas both actin and micro-
tubules concentrate apically concomitant with differential localization of membrane
and polarity protein complexes (Reeve and Kelly 1983 ; Johnson and Maro 1984 ;
Houliston and Maro 1989 ). Cell–cell contact appears to be essential for establishing
the orientation of polarity, since blastomeres polarize along the axis perpendicular
to cell contact and apical poles form farthest from the contact point. However,
additional mechanisms are also likely involved (Ziomek and Johnson 1980 ; Johnson
Fig. 4.11 Mammalian embryo compaction and blastulation. The processes of compaction, intra-
cellular adhesion, and polarization result in the formation of a morula at the eight-cell and 16- to
32-cell stage in mouse and human embryos, respectively. In mammals, compaction is mediated by
the development of adherens junctions and results in the development of the first developmental
asymmetry in the embryo. Once compaction is complete, the assembly of tight junctions in the
embryo initiates cavitation and the formation of a fluid-filled cavity called the blastocoel. Most
mammalian species, including humans, form blastocysts between days 5 and 6, whereas mouse
embryos begin blastulation earlier between days 3 and 4 and bovine embryos later between days 7
and 8
A. Hasley et al.