Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1168 Chapter 21: Development of Multicellular Organisms
that diffuse through the embryo from cell to cell, not by transcription regulators
that move through the cytoplasm of a syncytium. Not surprisingly, the Organizer
is now known to be a major source of secreted protein signals.
A Competition Between Secreted Signaling Proteins Patterns the
Vertebrate Embryo
The signal molecules that pattern the frog embryo along the animal-vegetal (A-V)
axis belong to the TGFβ family: they are secreted by a signaling center at the vegetal
pole and form concentration gradients along the A-V axis. The Nodal protein
acts over a relatively short range: cells near the vegetal pole are exposed to high
levels of it and respond by switching on genes that promote the development of
endoderm; cells further away are exposed to lower levels and activate genes that
promote the formation of mesoderm. The cells at the vegetal pole that produce
Nodal also produce a more rapidly diffusing TGFβ-like protein called Lefty, which
antagonizes Nodal. The result is a high ratio of Lefty to Nodal at the animal pole,
where Lefty predominates and Nodal signaling is blocked; this causes the cells
there to develop as ectoderm (Figure 21–30A). Thus, a mid-range activation by
Nodal, combined with a long-range inhibition by Lefty, sets up the pattern of progenitors
along the A-V axis for the three germ layers—endoderm, mesoderm, and
ectoderm.
The frog’s dorsal signaling system uses a different set of secreted signals from
that of the vegetal signaling system to subdivide the germ-layer territories according
to location along the D-V axis of the embryo. It exerts its influence by secreting
two inhibitory signal proteins, called Chordin and Noggin. These antagonize the
action of bone morphogenetic proteins (BMPs; members of yet another subclass
of the TGFβ family), which themselves are secreted throughout the embryo. In
this way, Chordin and Noggin form a dorsal-to-ventral gradient that blocks BMP
signaling on the dorsal side but allows it to remain high on the ventral side (Figure
21–30B). Ectodermal cells that experience high levels of BMP signaling are driven
to epidermal fates, whereas cells that experience little or no BMP signaling remain
neural.
Knowing the signals that specify the three germ layers and various tissue
types of the vertebrate body, one can reproduce this specification in a culture
dish. Frog cells taken from the animal-pole region of the embryo, for example,
ANIMAL Lefty
BMP ANIMAL
(inhibitor)
(activator)
Nodal
(activator)
V V
E ENTRAL
N
TR
A
L
D
O
RSAL
Chordin
(inhibitor)
Noggin
(inhibitor)
D
ORSAL
(A)
VEGETAL
resulting Nodal activity
frog embryo
(B)
VEGETAL
resulting BMP activity
Figure 21–30 How Nodal and bone
morphogenic protein (BMP) signaling
pattern the embryonic axes. Nodal and its
antagonist Lefty pattern the animal-vegetal
axis, while BMP and its antagonists Chordin
and Noggin pattern the dorsoventral axis.
(A) In the animal pole region, where Nodal
levels are low relative to Lefty, Lefty blocks
Nodal from binding to its receptors. In the
vegetal region, there is an excess of Nodal,
resulting in Nodal pathway activation.
(B) Along the dorsoventral axis, BMP is
widely present but Chordin and Noggin
are concentrated at the dorsal side: there,
they bind to BMP and block its binding to
receptors. The resulting patterns of Nodal
and BMP activity are illustrated at the
bottom of the figure.