Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants

Abstract

It is widely held that segregation of tissues expressing different cadherins results from cadherin-subtype-specific binding specificities. This belief is based largely upon assays in which cells expressing different cadherin subtypes aggregate separately when shaken in suspension. In various combinations of L cells expressing NCAM, E-, P-, N-, R-, or B-cadherin, coaggregation occurred when shear forces were low or absent but could be selectively inhibited by high shear forces. Cells expressing P- vs E-cadherin coaggregated and then demixed, one population enveloping the other completely. To distinguish whether this demixing was due to differences in cadherin affinities or expression levels, the latter were varied systematically. Cells expressing either cadherin at a lower level became the enveloping layer, as predicted by the Differential Adhesion Hypothesis. However, when cadherin expression levels were equalized, cells expressing P- vs E-cadherin remained intermixed. In this combination, "homocadherin" (E-E; P-P) and "heterocadherin" (E-P) adhesions must therefore be of similar strength. Cells expressing R- vs B-cadherin coaggregated but demixed to produce configurations of incomplete envelopment. This signifies that R- to B-cadherin adhesions must be weaker than either "homocadherin" adhesion. Together, cadherin quantity and affinity control tissue segregation and assembly through specification of the relative intensities of mature cell-cell adhesions.

Timing and kinetics of E‐ to N‐cadherin switch during neurulation in the avian embryo

“…Besides cell adhesion, one of the major roles of cadherins is to mediate cell recognition and segregation. Using transfected cell lines (Duguay et al, 2003) showed that sorting depends on both the type of cadherin expressed by the cells and its relative amount on the cell surface. Therefore, it is tempting to propose that the timing and kinetics of E-to N-cadherin switch during neurulation reflects the spatial segregation of the different lineages arising from the neurectoderm along the medio-lateral axis.…”

Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin

“…Decreased expression of E-cadherin results in a loss of cell-cell adhesion and increased cell migration and invasion (3). Cadherin-mediated cell-cell adhesion is modulated by changes in the level of cadherin on the cell surface (4,5).…”

Expression of classical cadherins in the cerebellar anlage: Quantitative and functional aspects

“…Indeed, in a system where cadherins alone mediate cell adhesion, quantitative aspects may be at least equally important for proper cell sorting as molecular differences between individual cadherins (Duguay et al, 2003). This notion is supported by recent findings which relate specific developmental disturbances to quantitative disturbances of N-cadherin expression levels (Kostetskii et al, 2001;Masai et al, 2003).…”

“…The differences in cadherin expression by immature granule cell precursors, their differentiating descendants, and Pax2-GFP-defined precursors of inhibitory interneurons suggests that cadherins might be involved in driving differential cell sorting and mixing, as predicted by the differential adhesion model (Duguay et al, 2003). Therefore, we analyzed the location of inhibitory interneuronal precursors versus that of cells of the granule cell lineage in reaggregate cultures.…”

“…Yet mechanistically, differences in cell adhesivity and behavior may not only be related to expression of distinct cadherins, but also to quantitative differences in expression of a given cadherin (Duguay et al, 2003;Foty and Steinberg, 2005). Indeed, in a system where cadherins alone mediate cell adhesion, quantitative aspects may be at least equally important for proper cell sorting as molecular differences between individual cadherins (Duguay et al, 2003).…”