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mals, with the appearance of the organizer and cell involution lagging behind that
of ventrolateral cell ingression (Fig. 6.14). It is possible that the lessened impor-
tance of cortical rotation-like mechanisms led to subtle reorganization of the orga-
nizer gene regulatory networks, causing organizer genes such as Noggin to be
expressed later relative to other dorsal genes.
Mammals exhibit the greatest changes in axis-forming mechanisms within the
vertebrates. There is also wide variation in these mechanisms within the mammals
themselves. Mammalian eggs have evolved to lose size and yolk content, as well as
any notable animal–vegetal asymmetry and cortical rotation-related events in the
process. The evolution of implantation also necessitated the early segregation of
embryonic and extra-embryonic lineages and the maintenance of embryonic pluri-
potency. Furthermore, gastrulation in mammals initiates with far fewer cells than in
other groups of organisms, ~250 cells in the mouse (compared with >10,000 in the
frog and chicken), and is accompanied by rapid cell division. This rapid cell cycle
of 2–6 h (Snow 1977 ) coincides with germ layer and axis patterning in the mam-
malian embryo, and has sparked evolutionary comparisons to the cleavage stage
cell cycle in more primitive animals (O'Farrell et al. 2004 ). Whether this rapid divi-
sion is indeed a conserved but temporally deferred event, as has been proposed, is
unclear. Alternatively, there may exist a general correlation between pluripotency
and shorter G1/G2 phases, with limited cell cycle checkpoints, as is seen in cultured
stem cells (Becker et al. 2006 ).
What are some future prospects for the study of axis formation? After many
decades of research, the ideas of symmetry breaking and self-organization in
development remain compelling yet incompletely understood. Indeed, the ideas of
self- organization and biological “regulation” predate the discovery of the orga-
nizer and have been developed into the concepts of the self-regulating embryonic
“field” and pattern formation by positional information (Child 1915 ; Weiss 1926 ;
Nieuwkoop 1967 ; Wolpert 1969 , 1971 ; Green and Sharpe 2015 ). The ability of the
organizer to undergo self-organization was noted by Spemann and others and
clearly implies a complex network of interactions. Recent work showing inverse
transcriptional regulation within the BMP regulatory circuitry has shed some light
onto these processes. This observation is only the first step toward understanding
self-organization at the gene regulatory network level, and additional general prin-
ciples are likely to be identified. Although the conserved transcriptional control of
genes like Goosecoid has long been noted, these mechanisms have not necessarily
been fully characterized or compared. Remarkably, large and robust organizer
gene regulatory networks have not yet been elucidated for any vertebrate organ-
ism. It should eventually be possible to generate comparative organizer gene regu-
latory networks across vertebrates and quantitatively compare their properties.
Such analyses might shed light on possible changes in relative onset of organizer
activity and also provide insight into the control of cell behaviors during gastrula-
tion, as there have been several evolutionary transitions between involution and
ingression in similar tissues.
Additionally, with regard to the complex interactions underlying symmetry break-
ing events in early vertebrate development, the molecular basis of microtubule orga-
D.W. Houston