Comparison of molecular mechanisms mediating cell contact phenomena in model developmental systems: an exploration of universality

Abstract

Are there universal molecular mechanisms associated with cell contact phenomena during metazoan ontogenesis? Comparison of adhesion systems in disparate model systems indicates the existence of unifying principles. Requirements for multicellularity are (a) the construction of three-dimensional structures involving a crucial balance between adhesiveness and motility; and (b) the establishment of integration at molecular, cellular, tissue, and organismal levels of organization. Mechanisms for (i) cell-cell and cell-substrate adhesion, (ii) cell movement, (iii) cell-cell communication, (iv) cellular responses, (v) regulation of these processes, and (vi) their integration with patterning, growth, and other developmental processes are all crucial to metazoan development, and must have been present for the emergence and radiation of Metazoa. The principal unifying themes of this review are the dynamics and regulation of cell contact phenomena. Our knowledge of the dynamic molecular mechanisms underlying cell contact phenomena remains fragmentary. Here we examine the molecular bases of cell contact phenomena using extant model developmental systems (representing a wide range of phyla) including the simplest i.e. sponges, and the eukaryotic protist Dictyostelium discoideum, the more complex Drosophila melanogaster, and vertebrate systems. We discuss cell contact phenomena in a broad developmental context. The molecular language of cell contact phenomena is complex; it involves a plethora of structurally and functionally diverse molecules, and diverse modes of intermolecular interactions mediated by protein and/or carbohydrate moieties. Reasons for this are presumably the necessity for a high degree of specificity of intermolecular interactions, the requirement for a multitude of different signals, and the apparent requirement for an increasingly large repertoire of cell contact molecules in more complex developmental systems, such as the developing vertebrate nervous system. However, comparison of molecular models for dynamic adhesion in sponges and in vertebrates indicates that, in spite of significant differences in the details of the way specific cell-cell adhesion is mediated, similar principles are involved in the mechanisms employed by members of disparate phyla. Universal requirements are likely to include (a) rapidly reversible intermolecular interactions; (b) low-affinity intermolecular interactions with fast on-off rates; (c) the compounding of multiple intermolecular interactions; (d) associated regulatory signalling systems. The apparent widespread employment of molecular mechanisms involving cadherin-like cell adhesion molecules suggests the fundamental importance of cadherin function during development, particularly in epithelial morphogenesis, cell sorting, and segregation of cells.

Cell speed, persistence and information transmission during signal relay and collective migration

“…This finding was surprising -we expected cells moving in groups to have distinct behaviors, as observed in simulations that explore the role of cell adhesion during early and late stages of morphogenesis (Palsson and Othmer, 2000;Palsson, 2008). Indeed, cell-cell adhesion sites might induce both biochemical and mechanical perturbations (Bowers-Morrow et al, 2004;Weijer, 2009). Our findings therefore establish that the intrinsic motility machinery, as well as the ability to migrate directionally, are innate properties of single cells that are maintained independently of additional external signals or cell-cell interactions.…”

Multiscale Modeling of Form and Function

“…Accordingly, cells use both cadherins and integrins to assemble into multicellular tissues, to distinguish and rapidly respond to external cues, and to amplify the signal to launch an appropriate and coordinated response. Tissues achieve this task by a series of evolutionarily conserved modules that are initiated through the adhesion sensor, transduced through a series of molecular switches, and propagated through amplifiers (21, 47, 48) (Fig. 3).…”

Ectosomes Released by Polymorphonuclear Neutrophils Induce a MerTK-dependent Anti-inflammatory Pathway in Macrophages

“…hormones, cytokines, chemokines), and small molecular mediators (e.g. nucleotides, bioactive lipids, nitric oxide ions) (1)(2)(3). However, recent evidence emphasizes the transfer of information by small vesicles released by one cell to its target cell (4,5).…”