ISSN:1422-6405    

DOI:10.1159/000147745

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:1422-6405    

DOI:10.1159/000147746

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:1422-6405    

DOI:10.1159/000147747

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Epithelium is the tissue phenotype of early embryos and primitive adults of the chordate phylum. A second tissue type, however, is produced by epithelial-mesenchymal transformation (EMT) in higher chordates, such as vertebrata. Mesenchymal cells have the ability, which true epithelia do not, to invade and migrate through the extracellular matrix (ECM) to create dramatic cell transpositions. The first-formed or primary mesenchymal cells in amniote vertebrates migrate from the primitive streak to differentiate into the mesodermal and endodermal epithelia. Definitive mesenchyme with connective tissue and muscle potentials arises from the epithelial mesoderm at about the same time as the neural crest mesenchyme forms from the ectoderm. Later on in embryogenesis. EMT is used to remodel unwanted epithelia, such as that of the palate medial edges. We discuss the mechanisms by which epithelial cells transform into mesenchyme and vice versa. On the one hand, cells activate putative mesenchymal master genes, turn off epithelial genes, and acquire motility machinery that allows them to interact in 3 dimensions (3D) with ECM via actin cortex while sliding their endoplasm into their new front ends. On the other hand, primary mesenchymal cells can reactivate epithelial regulatory genes, such as E-cadherin, turn off the motility machinery for invading ECM, and reexpress apical-basal polarity. We review the genes, such as FSPI, src, ras, andfos, that are activated in cells transforming to mesenchyme and the genes their neighbors activate to induce EMT, such as those for TGFβ, NT-3, and sonic hedgehog. Suspension in 3D collagen gels can induce adult epithelium to undergo EMT; α5βl integrin is activated on surfaces in contact with collagen, including apical surfaces that do not normally express integrins. In vivo, it is possible that pathological manipulations of a cell’s environment likewise induce EMT. Of the examples we give, the creation of invasive metastatic carcinoma cells by EMT is the most fearful. Interestingly, transfection of either metastatic cells or normal embryonic fibroblasts with the E-cadherin gene converts them to the epithelial phenotype. It may be possible in the future to manipulate the tissue phenotype of diseased cells to the advantage of the an

ISSN:1422-6405    

DOI:10.1159/000147748

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The functional units in most inductive and morphogenetic processes in the embryo are not single cells, but rather collectives of interacting cells that give rise to the tissues and organs. Cell adhesion molecules (CAMs) are involved in defining cell collectives and their borders as they interact during inductive events in morphogenesis. The expression patterns of CAMs are highly dynamic and changes are known to occur during epithelial-mesenchymal transformations. Alterations in CAM expression are correlated with changes in morphology. Conversely, experimentally induced changes in morphology result in changes in CAM expression. The structure, function, distribution, and control of CAM gene expression are presented in this review, and discussed with regard to their importance to normal developmental processes, particularly epithelial-mesenchymal transformations.

ISSN:1422-6405    

DOI:10.1159/000147749

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In recent years, analyses of the structure and function of membrane-intercalated adhesion molecules have shown them to play key roles in determining cellular phentoype. As expected, adhesion has an important role in regulating cellular positioning, but there is also compelling evidence that information transduced via adhesion molecules affects the differentiation status of cells. Cell surface adhesion molecules can be classified into a number of gene families, including immunoglobulins, cadherins, selectins, proteoglycans, and integrins. All of these types of molecule are co-expressed on most cells,” and therefore the overall contribution of adhesion to cell phenotype is likely to be a net effect of the individual contributions of each of these groups. In this review, we will focus on the role of the integrins, which appear to be particularly important mediators of cell migration and adhesion-dependent intracellular signalling. A great deal is now known about the extracellular faces of integrins, including their structure and ligand-binding mechanisms, and in recent years, our knowledge of integrin-dependent signalling via cytoplasmic domains has improved considerably. An emerging picture is one of a dynamic family of receptors than can be expressed in different states of activation. Alterations in activity are apparently mediated by conformational changes that can be induced from both outside and inside cells. In turn, these changes in activity have concomitant consequences for adhesion and signallin

ISSN:1422-6405    

DOI:10.1159/000147750

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Adhesion of cells to their neighbors or to the extracellular matrix has multiple effects on cell shape, dynamics and fate. The most obvious and direct one is the assembly of single cells into ordered multicellular tissues and organs. This process requires specific transmembrane adhesion molecules which mediate the binding to the external surface, cytoskeletal filaments which attach to the cytoplasmic faces of the adhesion site, and a submembrane plaque which interconnects the two. The co-assembly of these junctional domains is essential for the formation of stable cell adhesions with the proper mechanical properties. In addition, adhesive interactions have prominent, global consequences on cell behavior and fate, affecting such processes as differentiation, growth and survival. To gain insight into the molecular basis for both the local and global effects of adhesive interactions, we have chosen to focus on one specific junctional domain, the submembrane plaque of microfilament-bound adhesions, namely cell-cell and cell-matrix adherens junctions. Based on both biochemical and morphological evidence we would like to propose that the junctional plaque plays a key role in mediating and regulating transmembrane junctional interactions and adhesion-dependent signaling. It offers multiple modes of linkage between the cytoskeleton and the membrane, and its assembly can be controlled at either the biosynthetic or posttranslational levels. Furthermore, recent data demonstrate that the submembrane plaque is involved in the transduction of transmembrane signals. We will show that this structure is the residence of an array of signaling enzymes (mostly kinases), that its structure and composition may be affected by activation of various signaling systems, and that adhesion itself may activate specific signal transduction pathways.

ISSN:1422-6405    

DOI:10.1159/000147751

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The neural crest is the organ system whose presence defines vertebrates. The onset of migration of neural crest cells is an archetypal epithelium to mesenchyme transition (EMT), and this event identifies the cell lineage. Little is known yet of the establishment of the neural crest, although the zinc finger gene Slug seems to be involved in specifying EMT competence. The details, especially the temporal order of events in neural crest EMT, vary between different species and between different axial levels, but several important features have emerged from observations in situ and experiments in vitro and in vivo. EMT seems to be strongly associated with decrease in cell-cell adhesion, and particularly with loss of N-cadherin on the surface of neural crest cells at the time of onset of migration. The related adhesion molecule T-cadherin is also present, but correlated changes have not yet been described, while the unrelated adhesion molecule N-CAM also declines on neural crest cells, but with a time course unrelated to EMT. The extracellular matrix is also important: EMT-related changes in matrix receptor (i.e. integrin) activity are recorded in avian crest cells, while the nature of the matrix itself changes in urodele amphibians. Changes in cell shape and in cell motility also occur at the time of EMT, consistent with changes in the cytoskeleton. These concerted changes can be triggered by TGF-β family growth factors, of which dorsalin-1 appears particularly important. These may act through pathways involving controlled alterations in phosphorylation to effect the complex of responses that make up EMT. Although much remains to be understood, the spatiotemporal definability of this system makes it a very useful model for studying EMTs in general

ISSN:1422-6405    

DOI:10.1159/000147752

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The earliest example of epithelio-mesenchymal transformation during embrynic development is the generation of the third germ layer, the mesoderm, from the epiblast (or primitive ectoderm), which marks the beginning of gastrulation. Although it has been regarded as most likely that the principles of this transformation in invertebrates and lower vertebrates also apply to amniotes, morphological and molecular details of mesoderm formation in birds and, in particular, in mammals, which may support this assumption, have only recently been clarified. This chapter thus brings together the light- and electron-microscopical morphology of epithelio-mesenchymal transformation during initial mesoderm formation in the mammalian embryo. Cellular differentiation during this process with regard to the cytoskeleton, cell adhesion molecules and the extracellular matrix are also covered as are cell kinetic studies and the candidate growth factors and genes most likely to be involved in the regulation of mesoderm formation in mammals. Finally, a model is presented which summarizes these morphological and molecular changes and which links the promoting and inhibiting influences of regulatory factors to some of the changes observed durng epithelio-mesenchymal transformation.

ISSN:1422-6405    

DOI:10.1159/000147753

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:1422-6405    

DOI:10.1159/000147754

出版商:S. Karger AG    

年代:1995

数据来源: Karger