Cadherins play a crucial part in these cell-sorting processes during development. The appearance and disappearance of specific cadherins correlate with steps in embryonic development where cells regroup and change their contacts to create new tissue structures. In the vertebrate embryo, for example, changes in cadherin expression are seen when the neural tube forms and pinches off from the overlying ectoderm: neural tube cells lose E-cadherin and acquire other cadherins, including N-cadherin, while the cells in the overlying ectoderm continue to express E-cadherin (Figure 19–8A and B). Then, when the neural crest cells migrate away from the neural tube, these cadherins become scarcely detectable, and another cadherin (cadherin 7) appears that helps hold the migrating cells together as loosely associated cell groups (Figure 19–8C). Finally, when the cells aggregate to form a ganglion, they switch on expression of N-cadherin again. If N-cadherin is artificially overexpressed in the emerging neural crest cells, the cells fail to escape from the neural tube.
Studies with cultured cells further support the idea that the homophilic binding of cadherins controls these processes of tissue segregation. In a line of cultured fibroblasts called L cells, for example, cadherins are not expressed and the cells do not adhere to one another. When these cells are transfected with DNA encoding E-cadherin, E-cadherins on one cell bind to E-cadherins on another, resulting in cell–cell adhesion. If L cells expressing different cadherins are mixed together, they sort out and aggregate separately, indicating that different cadherins preferentially bind to their own type (Figure 19–9A), mimicking what happens when cells derived from tissues that express different cadherins are mixed together. A similar segregation of cells occurs if L cells expressing different amounts of the same cadherin are mixed together (Figure 19–9B). It therefore seems likely that both qualitative and quantitative differences in the expression of cadherins have a role in organizing tissues.
Figure 19–8 Changing patterns of cadherin expression during construction of the vertebrate nervous system. the figure shows cross sections of the early chick embryo, as the neural tube detaches from the ectoderm and then as neural  crest cells detach from the neural tube. (a, B) Immunofluorescence micrographs showing the developing neural tube labeled with antibodies against (a) E-cadherin (blue) and (B) N-cadherin (yellow). (C) as the patterns of gene expression change, the different groups of cells segregate from one another according to the cadherins they express. (Micrographs courtesy of Miwako Nomura and Masatoshi takeichi.) cell expressing high level of E-cadherin cell expressing low level of E-cadherin (B)
Figure 19–9 Cadherin-dependent cell sorting. Cells in culture can sort themselves out according to the type and level of cadherins they express. this can be visualized by labeling different populations of cells with dyes of different colors. (a) Cells expressing N-cadherin sort out from cells expressing E-cadherin. (B) Cells expressing high levels of E-cadherin sort out from cells expressing low levels of E-cadherin. the cells expressing high levels adhere more strongly and end up internally.
Epithelial–Mesenchymal transitions Depend on Control of Cadherins