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over the years by many of the key participants (Harland 1994 , 2008 ; Elinson and
Holowacz 1995 ; De Robertis and Sasai 1996 ; Harland and Gerhart 1997 ; Chang
and Hemmati- Brivanlou 1998 ; De Robertis et al. 2000 ; De Robertis 2006 , 2009 ;
Harland and Grainger 2011 ).
6.4.1 The Differentiation of Axial Mesoderm and the Role
of BMP Antagonism
It is clear from numerous studies that the formation of a ventral-to-dorsal BMP
activity gradient through extracellular antagonism underlies the main functions of
the organizer in dorsoventral axial patterning (Fig. 6.11a). BMPs are members of
the Tgfb superfamily of secreted growth factors. These function as dimers and acti-
vate heteromeric cell surface serine/threonine kinase receptors, resulting in the
phosphorylation of BMP-specific Smad transcription factors (Smad 1/5/8) (Chap. 7 ;
reviewed in Little and Mullins 2006 ; Ozair et al. 2012 ). BMPs are expressed in non-
organizer tissue, namely the ventrolateral regions in amphibians and posterior prim-
itive streak of the epiblast in chick and mouse. These molecules function in a
Chrd, Fst, NogBmp4/7Chrd, Fst, Nog
dvap
p-Smad1/5ep.a.n.c.
p.n.c.a bgscn.p.Bmp4/7Bmp4/7Cv2/BmperSzlChrd Tld/Bmp1Admp DorsalVentralgscFig. 6.11 Dorsoventral patterning of the gastrula. (a) Image of an early gastrula Xenopus embryo
(left image) showing gsc mRNA expression in the organizer region (purple). This area expresses
BMP antagonists Chrd, Fst, and Nog in a dorsoventral gradient (blue shading), and is complemen-
tary to a gradient of BMP signaling (red shading), resulting in a graded pattern of phospho-
Smad1/5 (p-Smad1/5). On the right is a late gastrula showing continued ventroposterior pattering
by BMP signaling, specifying in progressively later fashion (differing line thicknesses) the anterior
neural crest (a.n.c), posterior neural crest (p.n.c.) and epidermis (ep.), in addition to the underlying
germ layers (not shown). (b) Simplified network model of secreted protein interactions acting in
dorsoventral patterning. Chrd secreted by the organizer antagonizes Bmp activity, mediated by
Bmp4/7 ventrally and Admp within the organizer. Bmp activity inhibits chrd expression. Tld/
Bmp1 acts as a Chrd inhibitor via proteolysis; Szl is a Tld inhibitor, indirectly promoting Chrd
activity in the extreme ventral region (dotted arrow). The critical reciprocal control interactions
responsible for self-organization are indicated with blue lines; Bmp4/7 positively controls its own
expression but inhibits admp expression. Bmps also upregulate cv2/bmper, a ventral Bmp antago-
nist, and inhibit chrd dorsally. Model after De Robertis ( 2009 )
D.W. Houston