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organization and polarization of microtubules dorsally and the transport of dorsal-
izing determinants (Gerhart et al. 1989 ). Similar overall patterns are seen in primi-
tive fish (Clavert 1962 ), suggesting that axis specification through cortical rotation in
the fertilized egg is an ancestral condition in vertebrates.
By contrast, sauropsids (birds and reptiles) and more derived fish (teleost and
selachiians/dogfish) lack an obvious physical marker of dorsoventral polarity. These
eggs contain abundant yolk and undergo discoidal cleavage, and axis formation
occurs after significant cleavage in the blastoderm. In birds and reptiles, evidence
suggests that rotation of the egg during passage through the oviduct affects axis
formation in the blastoderm. Similar gravitational mechanisms were originally
thought to exist in dogfish and teleosts (Clavert 1962 ), although recently, mecha-
nisms involving cytoskeletal polarization in the cortex, analogous to the amphibian
cortical rotation have been found in teleosts (zebrafish and medaka).
With the exception of the egg-laying monotremes, which undergo discoidal cleav-
age and are likely similar to reptiles with regard to axial patterning, mammals repre-
sent a significant divergence from this broad trend. The eggs of therian mammals
have lost yolk, reverted to holoblastic cleavage (secondary holoblastic cleavage) and
evolved the blastocyst structure to facilitate implantation. Consequently, the first cell
fate decisions are centered on distinguishing the embryo proper from extraembryonic
lineages rather than on establishing bilateral symmetry. Axial patterning is thus rather
late, only becoming apparent after implantation, about a week into development.
Early blastomeres retain pluripotency for an extended time and axis formation
requires multiple reciprocal interactions with extraembryonic tissues.
Although there was evidence that formation of the organizer depended on polar-
ization of the egg, the mechanisms connecting the two were totally unknown to early
embryologists. Studies in amphibians unexpectedly found that the organizer was
itself formed through induction, rather than by inheriting gray crescent material. This
organizer-inducing activity was predominantly found in dorsovegetal cells of the
blastula, later termed the “Nieuwkoop center” after its discoverer, and its formation
depended on cortical rotation (Gerhart et al. 1989 ). These experiments were a critical
link in the chain of causality from egg to organizer and were represented in various
three- and four-signal models familiar to developmental biologists (Slack 1991 ). The
cortical rotation → Nieuwkoop center → organizer model has been a useful concep-
tual tool and has directed much of the research into the molecular basis for these
processes and their conservation across vertebrates. It is now appreciated that cortical
rotation results in dorsal Wnt/beta-catenin signaling, activating Transforming growth
factor beta (Tgfb)/Nodal signaling in the vegetal cells, which induce and pattern the
organizer in the overlying equatorial cells. Analogous mechanisms have been found
acting in the teleost dorsal yolk syncytial layer (dYSL) of the egg and in the avian
posterior marginal zone (PMZ) epiblast, based on molecular and functional data,
suggesting deep conservation of these processes in the early vertebrate lineage.
Recent cellular and molecular characterization of axis formation and patterning
has produced a wealth of examples of such deeply conserved vertebrate developmen-
tal mechanisms. Vertebrate embryology has historically been a comparative science,
with investigations encompassing a wide range of diverse organisms. More recently,
D.W. Houston