355fates are determined by the absolute dosage of Nodal to which a cell is exposed as
a function of their distance form the source of Nodal (Dyson and Gurdon 1998 ).
The classic morphogen gradient model could explain how the germ layers are
induced and patterned in amphibians, but is difficult to reconcile with certain features
of amniote and teleost embryos. The fate maps of fish, chicken, and mice show that
mesoderm and endodermal precursors are intermingled before gastrulation (Fig. 7.5b-
d) (Lawson et al. 1991 ; Warga and Nusslein-Volhard 1999 ; Lawson and Schoenwolf
2003 ; Hagos and Dougan 2007 ; Hagos et al. 2007 ). In zebrafish at this stage, cells
move in random directions as far as 70 μm (Bensch et al. 2013 ). Cells are first exposed
to Nodal signals at the margin during epiboly and conditional inactivation experi-
ments showed that Nodal signals are required during this window to specify cell fates
(Rebagliati et al. 1998a; Hagos and Dougan 2007 ; Hagos et al. 2007 ). In the mouse
and chicken, cells are first exposed to Nodal signals when they enter the primitive
streak and they are continually exposed to these signals as long as they remain in the
streak (Joubin and Stern 1999 ; Kinder et al. 2001 ). In both fish and chicken, germ
layer cell fates only become irreversibly determined during internalization, as shown
by transplant experiments (Ho and Kimmel 1993 ; Kimura et al. 2006 ).
AB
Nodal Antivin/LeftyC
NodalAntivin/LeftyNodalAntivin/Lefty
Vegetal PoleVegetal Pole
Fig. 7.11 Nodal reaction-diffusion mechanism. (a) Nodal signals induce their own expression as
well as that of their antagonist, Antivin/Lefty. (b) In the classic Morphogen Model, Antivin/Lefty
diffuses at a faster rate than Nodal, creating a gradient of Nodal signaling activity. Cells interpret
this gradient according to their position within the gradient, with high doses specifying endoderm
and lower levels specifying mesoderm. Cells adopt ectodermal fates in the complete absence of
Nodal signals. (c) The Temporal Gradient Model takes the cell movements of the blastoderm and
gastrula into account. The Reaction-Diffusion mechanism establishes a zone of Nodal signaling, in
which cells are exposed to different Nodal doses. Cells are exposed to Nodal signals for different
lengths of time depending on their movement path with respect to the Nodal gradient during the
blastoderm and gastrula stages. Cells adopt different fates according to the total cumulative dose
of Nodal signals to which they are exposed, as a function of the duration of their exposure and their
position within the Nodal gradient
7 Establishment of the Vertebrate Germ Layers