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

OVERVIEW OF DEVELOPMENT
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source of morphogen
morphogen
gradient forms
cellular response
to gradient
field of cells
Figure 21–8 Gradient formation and
interpretation. A gradient forms by
localized production of an inducer—a
morphogen—that diffuses away from
its source. Different concentrations of
morphogen (or different durations of
exposure) induce different gene expression
patterns and cell fates in responding cells.
Diffusive transport can generate gradients
only over short distances, and morphogens
generally act over distances of 1 mm or
less.
0.1 mm
histories to respond to the same signals differently (Figure 21–7B). Thus, the same
few signaling pathways can be used repeatedly at different times and places with
different outcomes, so as to generate patterns of unlimited complexity.
MBoC6 n22.205/22.08
Morphogens Are Long-Range Inductive Signals That Exert Graded
Effects
Signal molecules often govern simple yes–no choices—one outcome when
their concentration is high, another when it is low. In many cases, however, the
responses are more finely graded: a high concentration of a signal molecule may,
for example, direct cells into one developmental pathway, an intermediate concentration
into another, and a low concentration into yet another.
One common way to generate such different concentrations of a signal molecule
is for the molecule to diffuse out from a localized signaling source, creating
a concentration gradient. Cells at different distances from the source are driven
to behave in a variety of different ways, according to the signal concentration that
they experience (Figure 21–8). A signal molecule that imposes a pattern on a
whole field of cells in this way is called a morphogen. In the simplest case, a specialized
group of cells produces a morphogen at a steady rate, and the morphogen
is then degraded as it diffuses away from this source. The speed of diffusion and
the half-life of the morphogen will together determine the range and steepness of
its resulting gradient (Figure 21–9).
This simple mechanism can be modified in various ways. Receptors on the
surface of cells along the way, for example, may trap the diffusing morphogen and
cause it to be endocytosed and degraded, shortening its effective half-life. Alternatively,
the morphogen may bind to molecules in the extracellular matrix such as
heparan sulfate proteoglycan (discussed in Chapter 19), thereby greatly reducing
its diffusion rate.
Lateral Inhibition Can Generate Patterns of Different Cell Types
Morphogen gradients, and other kinds of inductive signal, exploit an existing
asymmetry in the embryo to create further asymmetries and differences between
cells: already, at the outset, some cells are specialized to produce the morphogen
and thereby impose a pattern on another class of cells that are sensitive to it. But
morphogen concentration
(A) (B) (C)
time from start increased signal diffusion increased signal stability
5 min
10 min
20 min
40 min
80 min
160 min
0 0.1 0.2 0 0.1 0.2 0
0.1 0.2
distance from source (mm)
Figure 21–9 Setting up a signal gradient
by diffusion. (A–C) Each graph shows six
successive stages in the buildup of the
concentration of a signal molecule that is
produced at a steady rate at the origin, with
production starting at time 0. In all cases,
the molecule undergoes degradation as
it diffuses away from the source, and the
graphs are calculated on the assumption
that diffusion is occurring along two axes in
space (for example, radially from a source
in an epithelial sheet). (A) The pattern of the
morphogen assuming that the molecule
has a half-life of 170 minutes, and that it
diffuses with an effective diffusion constant
of D = 1 μm 2 sec –1 , typical of a small
protein molecule in extracellular tissues.
Note that the gradient is already close to its
steady-state form within an hour and that
the concentration at steady state falls off
exponentially with distance. (B) A threefold
increase in the diffusion constant of the
morphogen extends its range but lowers its
concentration next to the source, whereas
(C) a threefold increase in morphogen halflife
increases its concentration throughout
the tissue. Effects of the morphogen will
depend not just on its concentration at
some critical moment, but also on how
each target cell integrates its response over
time. (Courtesy of Patrick Müller.)