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blastocyst. For technical reasons however, the specific contribution of vegetal blas-
tomeres could not be assessed in these studies. Mechanisms underlying this bias
may include epigenetic regulation of cell polarity (Parfitt and Zernicka-Goetz 2010 ),
decreased pluripotency transcription factor occupancy at target genes (Plachta et al.
2011 ) or a combination of factors. How this differential regulation is initiated is
unknown, but the lack of maternal influences and a lack of differential gene expres-
sion in two- and three-cell blastomeres (VerMilyea et al. 2011 ) suggest that this bias
is either an emergent property or a positioning effect in the four-cell stage embryo.
It is unclear at present whether any bias in early blastomere fate can be connected
to axis specification in the mammalian embryo. Although this will be discussed
further in Sect. 6.5.1 and similar to the bird embryo, the proximal events in mam-
malian axis formation involve the asymmetric migration of cells in the extraembry-
onic anterior visceral endoderm/hypoblast.

6.3 Initiation of Axis Induction by Dorsal Determinant

Signaling

Numerous models have been suggested for how early asymmetries in the egg and
embryo can lead to the specification of the organizer and ultimately to axis forma-
tion. Classical views, perhaps influenced by the importance of cytoplasmic localiza-
tions in invertebrates, suggested that the amphibian gray crescent contained
precursors or determinants of the organizer (Wilson 1928 ). Another influential idea
was that of a dorsal “cortical field” intersecting with a vegetal yolk gradient to deter-
mine the position of the organizer (Dalcq and Pasteels 1937 ). Later experiments
showed that mesoderm in general, and the organizer in particular, required inductive
cell–cell signaling by the vegetal prospective endoderm (see Chap. 7 ; Boterenbrood
and Nieuwkoop 1973 ; Gimlich and Gerhart 1984 ; Dale et al. 1985 ), suggesting that
cell-autonomous inheritance of organizer determinants was subordinate

polar body

zona pellucida ‘vegetal’ blastomere

trophectoderm

inner cell mass

2-cell stage 4-cell stage blastocyst

Fig. 6.6 Early bias of mouse blastomeres towards lineage fate but not axial polarity. Two-cell
blastomeres undergo rotational cleavage (dotted white lines indicate cleavage planes), generating
a fraction of embryos with a tetrahedral cell arrangement. In this formation, vegetal blastomeres
are biased towards contributing to the trophectoderm (dark gray) in the blastocyst. The corre-
sponding animal blastomeres are biased towards contributing to the inner cell mass (blue). After
Zernicka-Goetz et al. ( 2009 )

6 Vertebrate Axial Patterning: From Egg to Asymmetry