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These studies highlight major challenges that the cleavage-stage embryo, in these
and likely other vertebrate species, has to overcome. These include structures such as
spindle asters that are too small relative to the large early blastomeres, a limited
supply of cellular building blocks within a changing landscape of cell size and orga-
nization, and the requirement for cytoskeletal specializations adapted to very large
cells. We discuss how the vertebrate embryo appears to use simple rules to drive
development even under these limitations, such as the use of interphase astral micro-
tubules from a given cycle to orient the spindle for the following cell cycle or the use
of limiting inherited reagents, such as tubulin, to scale spindles according to cell size
in later-stage embryos. Such simple rules provide elegant solutions to overcome con-
straints associated with the transition from an egg into a three-dimensional embry-
onic blastula. Notably, we examine how a combination of cell shape-sensing cues,
including those from a microtubule exclusion zone at the furrow for the previous cell
cycle to orient the spindle, explain the sequence of blastomeric divisions leading to
the basic cell arrangement in both zebrafish and Xenopus embryos, and possibly
other vertebrates as well, though this remains to be determined. Interestingly,
dynamic changes in the embryonic developmental landscape contribute to develop-
mental decisions as they occur. For example, changes in cell dimensions in teleost
blastomeres likely result in the eventual shift of the spindle plane from a horizontal
(x–y) axis to a vertical (z) axis, generating a two-tiered blastula.
Although not as well studied, similar rules may exist across the range of verte-
brate species, for example, mechanisms for spindle scaling in mammals and mecha-
nisms of cleavage plane positioning in proto-vertebrates such as ascidians,
suggesting that cellular mechanisms involved are highly conserved. This hypothesis
is bolstered by examination of the phylogenetic distribution of major cleavage pat-
terns across vertebrates and their close relatives.
It is possible that a wide variety of cleavage patterns can be explained with the
same simple rules but with different initial parameters or conditions. For example,
the presence of yolk enriched in the vegetal pole in Xenopus likely creates a pulling
force bias on the spindle, resulting in the animal movement of the spindle and even-
tually an asymmetric cell division leading to a smaller animal pole cell and a larger
vegetal pole cell. As another example, a change in shape in the initial blastodisc
may lead to changes in the relative proportions of blastomere allocated to different
dimensions in the resulting blastula. Basic cell shape-sensing mechanisms also
interact with specialized cytoplasmic structures, such as the CAB in ascidians,
resulting in the generation of added cell cleavage pattern variation. The observed
embryonic patterns thus appear to be the outcome of a temporal sequence based on
initial embryonic conditions (starting shape, amount, and type of relevant factors) as
they are modified by ongoing cycles of cell division by the factors inherited by the
egg itself. Future studies will continue to address detailed mechanistic aspects that
drive these early embryonic processes and will also allow us to understand how
changes in various conditions and parameters lead to diversity in blastomere
arrangements encountered in different species. Cell cleavage pattern is a backdrop
on which cell fate decisions are overlain, and it will also be important to better
understand the interconnection between these two types of processes. Future studies
A. Hasley et al.