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ventrally and antagonized dorsally by organizer molecules. Additional support for
this model came from characterization of patterns of BMP activity, finding that
levels of phosphorylated active Smad1 were enriched ventrally and absent from the
organizer (Faure et al. 2000 ; Schohl and Fagotto 2002 ).
BMP antagonism derived from the organizer also patterns the convergent exten-
sion movements of the axial mesoderm (also see Sect. 6.6). High levels of BMP
inhibit convergent extension behavior in Xenopus (Graff et al. 1994 ), and in fish there
is evidence that BMP signaling inhibits expression of convergent extension- promoting
Wnt/PCP ligands, wnt11 and wnt5b (Myers et al. 2002 ). BMP signaling may also
inhibit dorsal mesoderm involution but this has not been extensively studied
(Nakayama et al. 1998 ). And, BMPs can promote epithelial-mesenchymal transitions
and ingression behavior, which occurs in more ventrolateral (non-organizer) meso-
derm. Thus, the production of secreted BMP antagonists is essential and largely suf-
ficient for the self-differentiation and morphogenesis of the organizer into notochord
mesoderm and for the patterning of the surrounding germ layers.
6.4.2 The Role of the Organizer and BMP Antagonism
in Neural Induction
Because of the historical link to early organizer studies and a general interest in the
development of the central nervous system, the role of the organizer in neural induc-
tion has received considerable attention. Also, conceptually, neural induction is
thought of differently from axis and mesendoderm induction. Mesoderm and endo-
derm are induced from ectoderm, whereas ectoderm develops if inducers are absent,
and can thus be considered the “default” germ layer. Surprisingly and perhaps
counter- intuitively, experiments in Xenopus suggested that neural, rather than epi-
dermal, was the default state of the ectoderm (Hemmati-Brivanlou and Melton
1997 ; Chang and Hemmati-Brivanlou 1998 ; Stern 2006 ; Ozair et al. 2012 ).
Inhibition of mesendoderm-inducing Tgfb signaling using dominant-negative
receptors or endogenous antagonists (Hemmati-Brivanlou and Melton 1994 ; Chang
and Harland 2007 ) or depletion of maternal vegt mRNA (Zhang et al. 1998 ) results
in neuroectoderm formation in all presumptive germ layers. Critical evidence for
the neural default model includes experiments indicating that BMPs induce epider-
mis in dissociated cells that would otherwise become neuralized, and that Nog,
Chrd and Fst act as direct neural inducers in ectoderm tissue by blocking BMP
signaling. Interestingly, these antagonists elicited only anterior neural fates, which
hinted at possible mechanisms of anteroposterior patterning by the organizer (dis-
cussion of this aspect will be deferred to the following section).
Whereas the central requirement for BMP antagonism is clear, the extent that
BMP inhibition alone is sufficient for neural induction is unclear. Studies in chick
and Xenopus have indicated that neural induction also requires Wnt antagonism
(Wilson et al. 2001 ; Pera et al. 2003 ; Fuentealba et al. 2007 ) as well as ongoing FGF
signaling (Linker and Stern 2004 ; Delaune et al. 2005 ; Marchal et al. 2009 ).
Subsequent experiments using different methodologies have suggested that FGF
D.W. Houston