Abstract
During early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why are differentiation and adhesion so tightly linked? It is now over 60 years since Conrad Waddington noted the remarkable "Constancy of the Wild Type” (Waddington in Nature 183: 1654–1655, 1959) yet we still do not fully understand the mechanisms that make development so reproducible. Conversely, we do not understand why directed differentiation of cells in a dish is sometimes unpredictable and difficult to control. It has long been suggested that cells make decisions as 'local cooperatives' rather than as individuals (Gurdon in Nature 336: 772–774, 1988; Lander in Cell 144: 955–969, 2011). Given that the cadherin family of adhesion molecules can simultaneously influence morphogenesis and signalling, it is tempting to speculate that they may help coordinate cell fate decisions between neighbouring cells in the embryo to ensure fidelity of patterning, and that the uncoupling of these processes in a culture dish might underlie some of the problems with controlling cell fate decisions ex-vivo. Here we review the expression and function of cadherins during early neural development and discuss how and why they might modulate signalling and differentiation as neural tissues are formed.
Highlights
In the late 1970s, Masatoshi Takeichi proposed that cell–cell adhesion in Chinese hamster cells was mediated by two processes: one calcium-independent and the other calciumdependent
Variations in amino acid composition and in rotation angle between adjacent CA/CDHL domains may account for differences in the number of calcium ions bound at the interface of these domains
These findings again implicate a specific role for E-cadherin in modulating signalling during embryonic development that may be independent of adhesion
Summary
Cadherins have classically been described as molecules that regulate calcium-dependent cell adhesion in metazoans [30–33]. Variations in amino acid composition and in rotation angle between adjacent CA/CDHL domains may account for differences in the number of calcium ions bound at the interface of these domains (three for mammalian cadherins, one for S. aureus SraP) Despite their presence in bacteria, archaea and Filozoa, CA/CDHL domain-containing proteins are not ubiquitous throughout eukaryotes. The reverse process is conceivable, with commensal, parasitic or pathogenic prokaryotic and SAR species potentially acquiring CA/CDHL domains from Filozoa Proteins containing these domains could in turn support interaction with host cell surfaces, as suggested by Gachon and colleagues for the nonagonal family of SAR cadherins [51]. Aside from regulating adhesion in Metazoa and in some prokaryotes [33, 40], it has been suggested that non-metazoan proteins containing CA/CDHL domains may regulate cell–cell interactions in feeding processes, pathogen-host interaction and cell aggregation events. When considering the role of cadherins during neural development, we should bear in mind that they may have acquired multiple functions over evolutionary time and may be acting as more than just adhesion molecules
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