The different types of cadherins enable different types of cells to cohere selectively: cells expressing one type of cadherin will maximize their contact with cells expressing the same cadherin and thereby segregate from other cells, creating specific tissue boundaries. Cell mixing can be inhibited and boundaries created and maintained in another way as well: cells of different types can sometimes actively repel one another. The bidirectional activation of Eph receptors and ephrins discussed in Chapter 15 often mediates such repulsion, acting at interfaces between different groups of cells to keep the groups from mixing, and repelling invasion by inappropriate visitors. Ephrin–Eph signaling operates, for example, at the boundaries of the rhombomeres discussed earlier. Neighboring rhombomeres express complementary combinations of ephrins and Eph receptors, and this keeps the cells in adjacent rhombomeres strictly segregated, with a boundary between them that is sharply defined (Figure 21–49).
Groups of Similar cells can perform Dramatic collective rearrangements
Cadherin-mediated cell sorting and ephrin–Eph-mediated repulsion exemplify how differences in cell-surface properties can drive tissue arrangements, causing cells that express different sets of genes to separate from one another. However, groups of cells that are all similar can also undergo dramatic rearrangements. During frog gastrulation, for example, cells in one region of the surface epithelium invaginate and migrate as a sheet into the interior of the embryo and converge toward the embryonic midline. The movement is driven mainly by an active rearrangement of the migrating cells, called convergent extension. Here the cells crawl over one another in a coordinated way, displacing their neighbors as they migrate, causing the cell sheet to narrow along one axis (converge) and elongate along another (extend). Strikingly, small, square fragments of tissue from the
Figure 21–49 Sorting out by repulsion. ephrin–eph signaling in hindbrain segmentation in a chick embryo. each pair of rhombomeres (segments in the hindbrain) is associated with a branchial arch (a modified gill rudiment) to which it sends innervation. rhombomeres are distinguished from one another by expression of different Hox genes (see Figure 21–32). Mutual repulsion (red bars) between cells that express ephrinB2 in rhombomere 4 and epha4 in rhombomere 5 creates a sharp boundary.
lamellipodia attempt to crawl on surfaces of neighboring cells, pulling them inward in direction of arrows appropriate region of the embryo, isolated in culture, will spontaneously narrow and elongate, just as they would in the embryo (Figure 21–50). The alignment of the cell movements depends on the same signaling pathway that is involved in generating planar cell polarity within developing epithelia, as we discuss next.
Cells within an epithelium always have an apical–basal polarity (discussed in Chapter 19), but the cells of many epithelia show an additional polarity at right angles to this axis: the cells are all arranged as if they had an arrow written on them, pointing in a specific direction in the plane of the epithelium. This type of polarity is called planar cell polarity. In the wing of a fly, for example, each epithelial cell has a tiny asymmetrical projection, called a wing hair, on its surface, and the hairs all point toward the tip of the wing. Similarly, in the inner ear of a vertebrate, each mechanosensory hair cell has a precisely oriented asymmetric bundle of actin-filled, rodlike protrusions called stereocilia sticking up from its apical plasma membrane as a detector of sound and of forces such as gravity. Tilting the bundle in one direction causes ion channels in the membrane to open, electrically activating the cell; tilting in the opposite direction has the opposite effect. For the ear to function properly, the hair cells must be oriented correctly. Planar cell polarity is also important in the respiratory tract, where every ciliated cell must orient the beating of its cilia so as to sweep mucus upward, away from the lungs.