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HOME :: CHAPTER 3 :: RECEPTOR GRADIENTS :: GRADIENT MODELS OF POSITIONAL INFORMATION |
Gradient Models of Positional Information
How can cells be informed of their position in the embryo and then use that information to differentiate into the appropriate cell type? One explanation proposes gradients of morphogenetic substances (Boveri 1901; Child 1941; Wolpert 1971). In these models, a soluble substance (morphogen) is posited to diffuse from a source (where it is produced) to a sink (where it is degraded), establishing a continuous range of concentrations within that region. Theoretical considerations (Crick 1970) suggest that such gradients could only function over relatively small distances, less than 100 cell diameters. In gradient models, the concentration of the morphogen changes over distance, the highest concentrations being near the source of the morphogen. The cells would have to have "sensors" that would respond differently to different concentrations of the gradient. If the morphogen was a transcription factor, then enhancer or promoter elements might bind the morphogen at different strengths (Figure 1). For example, if a morphogen was being made at the anterior of the body, the genes responsible for organizing head development might have an enhancer that would bind the morphogen poorly. Only when there was a large concentration of the morphogen present would that gene be active. The gene(s) responsible for thorax formation, on the other hand, might have an enhancer that would bind the morphogen rather well, enabling it to respond to relatively low levels of that morphogen. The cells of the head would express both these genes, while the cells of the thorax would express only that gene whose enhancer could bind low amounts of the morphogen. The cells in the posterior portion of the body would not see any of this morphogen, and neither of these genes would be activated. In this way, cells could sense the presence of a morphogen and respond differentially, depending on the morphogen concentration. The sensor would not have to be an enhancer; it could just as well be a cell-surface receptor for a specific growth factor (see Chapter 17).
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| Figure 1 A hypothetical model for gradients establishing positional information. The concentration of the morphogen drops with distance from the source. In this diagram, the receptors for the morphogen are enhancer elements of two genes that control cell fate, but the receptors could also be cytoplasmic receptors or membrane receptors. One of the receptors (in this case, the enhancer on gene A) needs a high concentration of morphogen in order to act. At high concentrations of morphogen, both genes A and B are active. In moderate concentrations, only gene B is active. Where the morphogen concentration falls below another threshold, neither gene is active. (After Wolpert 1971.) |
Most gradient models assume that all the cells that can respond to a gradient are equivalent. All these cells interpret the morphogen signal in the same way, and the concentration of morphogen that they receive determines their identity. However, the interpretation of gradients does not have to be linear. Take, for example, a series of exam grades that stretches uniformly from 100 to 60. In one scheme (a "linear" reading), a grade between 100 and 90 is A, 89–80 is B, 79–70 is C, and 69–60 is D. In another class (using a "curved" reading), 100–95 is A, 94–85 is B, 84–70 is C, and 69–60 is D. Nijhout (1981) has used a two-gradient model to explain the development of "eyespot" patterns on butterfly wings. One gradient consists of a linear diffusion of a morphogen. The second gradient involves the interpretation of this morphogen; in other words, the sensitivity threshold of the cells involved differs at different regions of the wing. The existence of the second gradient gives rise to an elliptical spot, not the circular spot that would result if the sensitivity gradient were absent (Figure 2).
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| Figure 2 Gradient model of positional information proposed to explain butterfly wing spots. (A) Photograph of an eyespot on the wing of Morpho peleides. (B) Diagram of a two-gradient model that may explain the way the spot was generated. The origin of the morphogen is at the center of the spot and corresponds to the apex of a cone, the height of which reflects its concentration. Concentration Q represents the level of morphogen needed to reach the threshold sensitivity for the formation of color in those wing cells. (C) Photograph of the wing of Smyrna blomfildia, in which the eyespots are elliptical. (D) Different orientations of the sensitivity gradient Q could result in such elliptical eyespots. (After Nijhout 1981, courtesy of H. F. Nijhout.) |
Literature Cited
Boveri, T. 1901. Über die Polarität des Seeigeleiers. Eisverh. Phys. Med. Ges. Würzburg 34: 145-175.
Child, C. M. 1941. Patterns and Problems of Development. University of Chicago Press, Chicago.
Crick, F. H. C. 1970. Diffusion in embryogenesis. Nature 225: 420-422.
Nijhout, H. F. 1981. The color patterns of butterflies and moths. Sci. Am. 245 (5): 140-151.
Wolpert, L. 1971. Positional information and pattern formation. Curr. Top. Dev. Biol. 6: 183-224.
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HOME :: CHAPTER 3 :: RECEPTOR GRADIENTS :: GRADIENT MODELS OF POSITIONAL INFORMATION |