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 0 0.1 0.2 0 0.1 0.2 0 0.1 0.2 distance from source (mm)
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.
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 μm2 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 half-life 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.)