RESUMEN
Convergent extension of the chordamesoderm is the best-examined gastrulation movement in Xenopus. Here we study general features of cell-cell contacts in this tissue by combining depletion of adhesion factors C-cadherin, Syndecan-4, fibronectin, and hyaluronic acid, the analysis of respective contact width spectra and contact angles, and La3+ staining of the pericellular matrix. We provide evidence that like in other gastrula tissues, cell-cell adhesion in the chordamesoderm is largely mediated by different types of pericellular matrix. Specific glycocalyx structures previously identified in Xenopus gastrula tissues are absent in chordamesoderm but other contact types like 10-20 nm wide La3+ stained structures are present instead. Knockdown of any of the adhesion factors reduces the abundance of cell contacts but not the average relative adhesiveness of the remaining ones: a decrease of adhesiveness at low contact widths is compensated by an increase of contact widths and an increase of adhesiveness proportional to width. From the adhesiveness-width relationship, we derive a model of chordamesoderm cell adhesion that involves the interdigitation of distinct pericellular matrix units. Quantitative description of pericellular matrix deployment suggests that reduced contact abundance upon adhesion factor depletion is correlated with excessive accumulation of matrix material in non-adhesive gaps and the loss of some contact types.
Asunto(s)
Gástrula , Notocorda , Animales , Gástrula/metabolismo , Xenopus laevis , Gastrulación , Adhesión Celular , Movimiento CelularRESUMEN
Morphogenetic movements during animal development involve repeated making and breaking of cell-cell contacts. Recent biophysical models of cell-cell adhesion integrate adhesion molecule interactions and cortical cytoskeletal tension modulation, describing equilibrium states for established contacts. We extend this emerging unified concept of adhesion to contact formation kinetics, showing that aggregating Xenopus embryonic cells rapidly achieve Ca2+-independent low-contact states. Subsequent transitions to cadherin-dependent high-contact states show rapid decreases in contact cortical F-actin levels but slow contact area growth. We developed a biophysical model that predicted contact growth quantitatively from known cellular and cytoskeletal parameters, revealing that elastic resistance to deformation and cytoskeletal network turnover are essential determinants of adhesion kinetics. Characteristic time scales of contact growth to low and high states differ by an order of magnitude, being at a few minutes and tens of minutes, respectively, thus providing insight into the timescales of cell-rearrangement-dependent tissue movements.
Asunto(s)
Cadherinas , Gástrula , Animales , Adhesión Celular , Xenopus laevis , Gástrula/metabolismo , Cadherinas/metabolismo , Moléculas de Adhesión CelularRESUMEN
The control of cell-cell adhesion and detachment is essential for collective migration and cell rearrangement. Here, we have used the contact behavior of Xenopus gastrula mesoderm explants migrating directionally on ectoderm conditioned substratum to study the regulation of active cell-cell detachment. When colliding laterally, explants repelled each other, whereas they fused front-to-back when aligned in the direction of migration. For this mesoderm polarization by the substratum, we identified three control modules. First, PDGF-A signaling normally suppresses contact-induced collapse of lamellipodia in a polarized manner. Disruption of PDGF-A function, or of Xwnt6, decreased the polarization of explant contact behavior. Second, the Wnt receptor Xfz7 acted upstream of the kinase Pak1 to control explant fusion independently of PDGF-A-promoted lamellipodia stability. Third, ephrinB1 acted with Dishevelled (Dvl) in front-to-back explant fusion. The second and third modules have been identified previously as regulators of tissue separation at the ectoderm-mesoderm boundary. On non-polarizing, fibronectin-coated substratum, they controlled repulsion between explants in the same way as between tissues during boundary formation. However, explant repulsion/fusion responses were reversed on conditioned substratum by the endogenous guidance cues that also control oriented contact inhibition of lamellipodia. Together, control modules and substratum-bound guidance cues combine preferential front-back adhesion and diminished lateral adhesion of cells to promote collective directional mesoderm migration.
Asunto(s)
Gástrula , Mesodermo , Animales , Gástrula/metabolismo , Xenopus laevis/metabolismo , Mesodermo/metabolismo , Adhesión Celular , Transducción de Señal , Movimiento Celular/fisiologíaRESUMEN
In the primitive vertebrate gastrula, the boundary between ectoderm and mesoderm is formed by Brachet's cleft. Here we examine Brachet's cleft and its control by Eph/ephrin signaling in Xenopus at the ultrastructural level and by visualizing cortical F-actin. We infer cortical tension ratios at tissue surfaces and their interface in normal gastrulae and after depletion of receptors EphB4 and EphA4 and ligands ephrinB2 and ephrinB3. We find that cortical tension downregulation at cell contacts, a normal process in adhesion, is asymmetrically blocked in the ectoderm by Eph/ephrin signals from the mesoderm. This generates high interfacial tension that can prevent cell mixing across the boundary. Moreover, it determines an asymmetric boundary structure that is suited for the respective roles of ectoderm and mesoderm, as substratum and as migratory layers. The Eph and ephrin isoforms also control different cell-cell contact types in ectoderm and mesoderm. Respective changes of adhesion upon isoform depletion affect adhesion at the boundary to different degrees but usually do not prohibit cleft formation. In an extreme case, a new type of cleft-like boundary is even generated where cortical tension is symmetrically increased on both sides of the boundary.
Asunto(s)
Efrinas , Gástrula , Animales , Ectodermo/metabolismo , Efrinas/metabolismo , Gástrula/metabolismo , Mesodermo/metabolismo , Xenopus laevis/metabolismoRESUMEN
The planar cell polarity pathway regulates cell polarity, adhesion, and rearrangement. Its cytoplasmic core components Prickle (Pk) and Dishevelled (Dvl) often localize as dense puncta at cell membranes to form antagonizing complexes and establish cell asymmetry. In vertebrates, Pk and Dvl have been implicated in actomyosin cortex regulation, but the mechanism of how these proteins control cell mechanics is unclear. Here we demonstrate that in Xenopus prechordal mesoderm cells, diffusely distributed, cytoplasmic Pk1 up-regulates the F-actin content of the cortex. This counteracts cortex down-regulation by Dvl2. Both factors act upstream of casein kinase II to increase or decrease cortical tension. Thus, cortex modulation by Pk1 and Dvl2 is translated into mechanical force and affects cell migration and rearrangement during radial intercalation in the prechordal mesoderm. Pk1 also forms puncta and plaques, which are associated with localized depletion of cortical F-actin, suggesting opposite roles for diffuse and punctate Pk1.
Asunto(s)
Actinas , Polaridad Celular , Proteínas de Unión al ADN , Proteínas con Dominio LIM , Proteínas de Xenopus , Actinas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Polaridad Celular/fisiología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Dishevelled/genética , Proteínas Dishevelled/metabolismo , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Xenopus , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismoRESUMEN
The morphogenic process of convergent thickening (CT) was originally described as the mediolateral convergence and radial thickening of the explanted ventral involuting marginal zone (IMZ) of Xenopus gastrulae (Keller and Danilchik, 1988). Here, we show that CT is expressed in all sectors of the pre-involution IMZ, which transitions to expressing convergent extension (CE) after involution. CT occurs without CE and drives symmetric blastopore closure in ventralized embryos. Assays of tissue affinity and tissue surface tension measurements suggest CT is driven by increased interfacial tension between the deep IMZ and the overlying epithelium. The resulting minimization of deep IMZ surface area drives a tendency to shorten the mediolateral (circumblastoporal) aspect of the IMZ, thereby generating tensile force contributing to blastopore closure (Shook et al., 2018). These results establish CT as an independent force-generating process of evolutionary significance and provide the first clear example of an oriented, tensile force generated by an isotropic, Holtfreterian/Steinbergian tissue affinity change.
Asunto(s)
Evolución Biológica , Gástrula , Animales , Movimiento Celular , Morfogénesis , Xenopus laevisRESUMEN
Molecular and structural facets of cell-cell adhesion have been extensively studied in monolayered epithelia. Here, we perform a comprehensive analysis of cell-cell contacts in a series of multilayered tissues in the Xenopus gastrula model. We show that intercellular contact distances range from 10 to 1,000 nm. The contact width frequencies define tissue-specific contact spectra, and knockdown of adhesion factors modifies these spectra. This allows us to reconstruct the emergence of contact types from complex interactions of the factors. We find that the membrane proteoglycan Syndecan-4 plays a dominant role in all contacts, including narrow C-cadherin-mediated junctions. Glypican-4, hyaluronic acid, paraxial protocadherin, and fibronectin also control contact widths, and unexpectedly, C-cadherin functions in wide contacts. Using lanthanum staining, we identified three morphologically distinct forms of glycocalyx in contacts of the Xenopus gastrula, which are linked to the adhesion factors examined and mediate cell-cell attachment. Our study delineates a systematic approach to examine the varied contributions of adhesion factors individually or in combinations to nondiscrete and seemingly amorphous intercellular contacts.
Asunto(s)
Cadherinas/metabolismo , Adhesión Celular , Comunicación Celular , Embrión no Mamífero/fisiología , Gástrula/fisiología , Proteínas de Xenopus/metabolismo , Animales , Cadherinas/genética , Embrión no Mamífero/citología , Gástrula/citología , Glicocálix/metabolismo , Proteínas de Xenopus/genética , Xenopus laevisRESUMEN
During Xenopus gastrulation, leading edge mesendoderm (LEM) advances animally as a wedge-shaped cell mass over the vegetally moving blastocoel roof (BCR). We show that close contact across the BCR-LEM interface correlates with attenuated net advance of the LEM, which is pulled forward by tip cells while the remaining LEM frequently separates from the BCR. Nevertheless, lamellipodia persist on the detached LEM surface. They attach to adjacent LEM cells and depend on PDGF-A, cell-surface fibronectin and cadherin. We argue that active cell motility on the LEM surface prevents adverse capillary effects in the liquid LEM tissue as it moves by being pulled. It counters tissue surface-tension effects with oriented cell movement and bulges the LEM surface out to keep it close to the curved BCR without attaching to it. Proximity to the BCR is necessary, in turn, for the maintenance and orientation of lamellipodia that permit mass cell movement with minimal substratum contact. Together with a similar process in epithelial invagination, vertical telescoping, the cell movement at the LEM surface defines a novel type of cell rearrangement: vertical shearing.
Asunto(s)
Movimiento Celular/fisiología , Gastrulación/fisiología , Mesodermo/fisiología , Xenopus laevis/fisiología , Animales , Cadherinas/metabolismo , Acción Capilar , Adhesión Celular/fisiología , Endodermo/metabolismo , Endodermo/fisiología , Fibronectinas/metabolismo , Gástrula/metabolismo , Gástrula/fisiología , Mesodermo/metabolismo , Seudópodos/metabolismo , Seudópodos/fisiología , Xenopus laevis/metabolismoRESUMEN
The Brachyury gene encodes a transcription factor that is conserved across all animals. In non-chordate metazoans, brachyury is primarily expressed in ectoderm regions that are added to the endodermal gut during development, and often form a ring around the site of endoderm internalization in the gastrula, the blastopore. In chordates, this brachyury ring is conserved, but the gene has taken on a new role in the formation of the mesoderm. In this phylum, a novel type of mesoderm that develops into notochord and somites has been added to the ancestral lateral plate mesoderm. Brachyury contributes to a shift in cell fate from neural ectoderm to posterior notochord and somites during a major lineage segregation event that in Xenopus and in the zebrafish takes place in the early gastrula. In the absence of this brachyury function, impaired formation of posterior mesoderm indirectly affects the gastrulation movements of peak involution and convergent extension. These movements are confined to specific regions and stages, leaving open the question why brachyury expression in an extensive, coherent ring, before, during and after gastrulation, is conserved in the two species whose gastrulation modes differ considerably, and also in many other metazoan gastrulae of diverse structure.
Asunto(s)
Ectodermo/crecimiento & desarrollo , Proteínas Fetales/genética , Gástrula/crecimiento & desarrollo , Morfogénesis/genética , Proteínas de Dominio T Box/genética , Animales , Endodermo/crecimiento & desarrollo , Proteínas Fetales/ultraestructura , Mesodermo/crecimiento & desarrollo , Notocorda/crecimiento & desarrollo , Proteínas de Dominio T Box/ultraestructura , Xenopus laevis/genética , Xenopus laevis/crecimiento & desarrollo , Pez Cebra/genética , Pez Cebra/crecimiento & desarrolloRESUMEN
Mesoderm and endoderm internalization in the Xenopus embryo are based on a number of region-specific morphogenetic processes that co-act in the vegetal half of the gastrula. In the multilayered wall surrounding the blastocoel, the apical layer engages in bottle cell formation and associated invagination and involution movements, and in cell intercalation in the plane of the layer. Of these epithelial-type processes, only bottle cell formation has been analyzed mechanistically. In the deep layers of the blastocoel wall, cell-on-cell migration drives the internalization of mesoderm by various forms of involution and of the endodermal cell mass by vegetal rotation. In the mesoderm, cells migrate in a mesenchymal mode with the aid of locomotory protrusions, whereas cells of the vegetal cell mass resemble free bottle cells that engage in ingression-type amoeboid migration. Cells rearrange by differential migration leading to parallel or orthogonal forms of intercalation and respective types of convergent extension. The interaction of the various apical and deep layer processes gives rise to dorsal multilayer invagination, ventrolateral internal involution, peak involution and orthogonal convergent extension of the dorsal posterior mesoderm, vegetal rotation, and blastopore constriction. It is speculated how these multilayer gastrulation movements could be derived from mechanisms in invertebrate single-epithelium gastrulae.
Asunto(s)
Embrión no Mamífero/fisiología , Endodermo/fisiología , Regulación del Desarrollo de la Expresión Génica , Mesodermo/fisiología , Morfogénesis , Proteínas de Xenopus/metabolismo , Xenopus laevis/fisiología , Animales , Movimiento Celular , Embrión no Mamífero/citología , Endodermo/citología , Mesodermo/citología , Transducción de Señal , Proteínas de Xenopus/genética , Xenopus laevis/embriologíaRESUMEN
Trogocytosis, in which cells nibble away parts of neighboring cells, is an intercellular cannibalism process conserved from protozoa to mammals. Its underlying molecular mechanisms are not well understood and are likely distinct from phagocytosis, a process that clears entire cells. Bi-directional contact repulsion induced by Eph/ephrin signaling involves transfer of membrane patches and full-length Eph/ephrin protein complexes between opposing cells, resembling trogocytosis. Here, we show that the phagocytic adaptor protein Gulp1 regulates EphB/ephrinB trogocytosis to achieve efficient cell rearrangements of cultured cells and during embryonic development. Gulp1 mediates trogocytosis bi-directionally by dynamic engagement with EphB/ephrinB protein clusters in cooperation with the Rac-specific guanine nucleotide exchange factor Tiam2. Ultimately, Gulp1's presence at the Eph/ephrin cluster is a prerequisite for recruiting the endocytic GTPase dynamin. These results suggest that EphB/ephrinB trogocytosis, unlike other trogocytosis events, uses a phagocytosis-like mechanism to achieve efficient membrane scission and engulfment.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Efrinas/metabolismo , Receptores de la Familia Eph/metabolismo , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Animales , Células Cultivadas , Células HEK293 , Células HeLa , Humanos , Ratones , Células 3T3 NIH , Transducción de SeñalRESUMEN
Cell-cell adhesion strength, measured as tissue surface tension, spans an enormous 1000-fold range when different cell types are compared. However, the examination of basic mechanical principles of cell adhesion indicates that cadherin-based and related mechanisms are not able to promote the high-strength adhesion experimentally observed in many late embryonic or malignant tissues. Therefore, the hypothesis is explored that the interaction of the pericellular matrices of cells generates strong adhesion by a mechanism akin to the self-adhesion/self-healing of dynamically cross-linked hydrogels. Quantitative data from biofilm matrices support this model. The mechanism links tissue surface tension to pericellular matrix stiffness. Moreover, it explains the wide, matrix-filled spaces around cells in liquid-like, yet highly cohesive, tissues, and it rehabilitates aspects of the original interpretation of classical cell sorting experiments, as expressed in Steinberg's differential adhesion hypothesis: that quantitative differences in adhesion energies between cells are sufficient to drive sorting.
Asunto(s)
Adhesión Celular , Comunicación Celular , Movimiento Celular , Matriz Extracelular/metabolismo , Modelos Biológicos , Animales , HumanosRESUMEN
Xenopus gastrulation movements are in large part based on the rearrangement of cells by differential cell-on-cell migration within multilayered tissues. Different patterns of migration-based cell intercalation drive endoderm and mesoderm internalization and their positioning along their prospective body axes. C-cadherin, fibronectin, integrins, and focal contact components are expressed in all gastrula cells and play putative roles in cell-on-cell migration, but their actual functions in this respect are not yet understood. The gastrula can be subdivided into two motility domains, and in the vegetal, migratory domain, two modes of cell migration are discerned. Vegetal endoderm cells show ingression-type migration, a variant of amoeboid migration characterized by the lack of locomotory protrusions and by macropinocytosis as a mechanism of trailing edge resorption. Mesendoderm and prechordal mesoderm cells use lamellipodia in a mesenchymal mode of migration. Gastrula cell motility can be dissected into traits, such as cell polarity, adhesion, mobility, or protrusive activity, which are controlled separately yet in complex, combinatorial ways. Cells can instantaneously switch between different combinations of traits, showing plasticity as they respond to substratum properties. This article is categorized under: Early Embryonic Development > Gastrulation and Neurulation.
Asunto(s)
Tipificación del Cuerpo/genética , Ectodermo/citología , Endodermo/citología , Gástrula/citología , Mesodermo/citología , Xenopus laevis/embriología , Animales , Cadherinas/genética , Cadherinas/metabolismo , Movimiento Celular , Polaridad Celular , Ectodermo/crecimiento & desarrollo , Ectodermo/metabolismo , Embrión no Mamífero , Endodermo/crecimiento & desarrollo , Endodermo/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Gástrula/crecimiento & desarrollo , Gástrula/metabolismo , Gastrulación/genética , Regulación del Desarrollo de la Expresión Génica , Integrinas/genética , Integrinas/metabolismo , Mesodermo/crecimiento & desarrollo , Mesodermo/metabolismo , Seudópodos/genética , Seudópodos/metabolismo , Seudópodos/ultraestructura , Transducción de Señal , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevis/genética , Xenopus laevis/crecimiento & desarrollo , Xenopus laevis/metabolismoRESUMEN
The leading-edge mesendoderm (LEM) of the Xenopus gastrula moves as an aggregate by collective migration. However, LEM cells on fibronectin in vitro show contact inhibition of locomotion by quickly retracting lamellipodia upon mutual contact. We found that a fibronectin-integrin-syndecan module acts between p21-activated kinase 1 upstream and ephrin B1 downstream to promote the contact-induced collapse of lamellipodia. To function in this module, fibronectin has to be present as puncta on the surface of LEM cells. To overcome contact inhibition in LEM cell aggregates, PDGF-A deposited in the endogenous substratum of LEM migration blocks the fibronectin-integrin-syndecan module at the integrin level. This stabilizes lamellipodia preferentially in the direction of normal LEM movement and supports cell orientation and the directional migration of the coherent LEM cell mass.
Asunto(s)
Movimiento Celular/fisiología , Inhibición de Contacto/fisiología , Mesodermo/embriología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Proteínas de Xenopus/metabolismo , Quinasas p21 Activadas/metabolismo , Animales , Mesodermo/citología , Factor de Crecimiento Derivado de Plaquetas/genética , Proteínas de Xenopus/genética , Xenopus laevis , Quinasas p21 Activadas/genéticaRESUMEN
During amphibian gastrulation, presumptive endoderm is internalised as part of vegetal rotation, a large-scale movement that encompasses the whole vegetal half of the embryo. It has been considered a gastrulation process unique to amphibians, but we show that at the cell level, endoderm internalisation exhibits characteristics reminiscent of bottle cell formation and ingression, known mechanisms of germ layer internalisation. During ingression proper, cells leave a single-layered epithelium. In vegetal rotation, the process occurs in a multilayered cell mass; we refer to it as ingression-type cell migration. Endoderm cells move by amoeboid shape changes, but in contrast to other instances of amoeboid migration, trailing edge retraction involves ephrinB1-dependent macropinocytosis and trans-endocytosis. Moreover, although cells are separated by wide gaps, they are connected by filiform protrusions, and their migration depends on C-cadherin and the matrix protein fibronectin. Cells move in the same direction but at different velocities, to rearrange by differential migration.
Asunto(s)
Endodermo/citología , Gástrula/citología , Xenopus laevis/embriología , Animales , Movimiento Celular , Embrión no Mamífero/citología , Endodermo/embriología , Endodermo/metabolismo , Gástrula/metabolismo , Xenopus laevis/metabolismoRESUMEN
Fluid-filled interstitial gaps are a common feature of compact tissues held together by cell-cell adhesion. Although such gaps can in principle be the result of weak, incomplete cell attachment, adhesion is usually too strong for this to occur. Using a mechanical model of tissue cohesion, we show that, instead, a combination of local prevention of cell adhesion at three-cell junctions by fluidlike extracellular material and a reduction of cortical tension at the gap surface are sufficient to generate stable gaps. The size and shape of these interstitial gaps depends on the mechanical tensions between cells and at gap surfaces, and on the difference between intracellular and interstitial pressures that is related to the volume of the interstitial fluid. As a consequence of the dependence on tension/tension ratios, the presence of gaps does not depend on the absolute strength of cell adhesion, and similar gaps are predicted to occur in tissues of widely differing cohesion. Tissue mechanical parameters can also vary within and between cells of a given tissue, generating asymmetrical gaps. Within limits, these can be approximated by symmetrical gaps.
Asunto(s)
Líquido Extracelular/metabolismo , Fenómenos Mecánicos , Modelos Biológicos , Animales , Fenómenos Biomecánicos , Adhesión Celular , Matriz Extracelular/metabolismoRESUMEN
The ectoderm of the Xenopus embryo is permeated by a network of channels that appear in histological sections as interstitial gaps. We characterized this interstitial space by measuring gap sizes, angles formed between adjacent cells, and curvatures of cell surfaces at gaps. From these parameters, and from surface-tension values measured previously, we estimated the values of critical mechanical variables that determine gap sizes and shapes in the ectoderm, using a general model of interstitial gap mechanics. We concluded that gaps of 1-4 µm side length can be formed by the insertion of extracellular matrix fluid at three-cell junctions such that cell adhesion is locally disrupted and a tension difference between cell-cell contacts and the free cell surface at gaps of 0.003 mJ/m2 is generated. Furthermore, a cell hydrostatic pressure of 16.8 ± 1.7 Pa and an interstitial pressure of 3.9 ± 3.6 Pa, relative to the central blastocoel cavity of the embryo, was found to be consistent with the observed gap size and shape distribution. Reduction of cell adhesion by the knockdown of C-cadherin increased gap volume while leaving intracellular and interstitial pressures essentially unchanged. In both normal and adhesion-reduced ectoderm, cortical tension of the free cell surfaces at gaps does not return to the high values characteristic of the free surface of the whole tissue.
Asunto(s)
Ectodermo/citología , Embrión no Mamífero/citología , Líquido Extracelular/metabolismo , Fenómenos Mecánicos , Xenopus laevis/embriología , Animales , Fenómenos Biomecánicos , Cadherinas/metabolismo , Presión , Proteínas de Xenopus/metabolismoRESUMEN
Adhesion differences are the main driver of cell sorting and related processes such as boundary formation or tissue positioning. In the early amphibian embryo, graded variations in cadherin density and localized expression of adhesion-modulating factors are associated with regional differences in adhesive properties including overall adhesion strength. The role of these differences in embryonic boundary formation has not been studied extensively, but available evidence suggests that adhesion strength differentials are not essential. On the other hand, the inside-out positioning of the germ layers is correlated with adhesion strength, although the biological significance of this effect is unclear. By contrast, the positioning of dorsal mesoderm tissues along the anterior-posterior body axis is essential for axis elongation, but the underlying sorting mechanism is not correlated with adhesion strength, and may rely on specific cell adhesion. Formation of the ectoderm-mesoderm boundary is the best understood sorting related process in the frog embryo. It relies on contact-induced cell repulsion at the tissue interface, driven by Eph-ephrin signaling and paraxial protocadherin-dependent self/non-self recognition.
Asunto(s)
Ectodermo/metabolismo , Endodermo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Mesodermo/metabolismo , Proteínas de Xenopus/genética , Xenopus laevis/embriología , Animales , Cadherinas/genética , Cadherinas/metabolismo , Adhesión Celular , Comunicación Celular , Movimiento Celular , Ectodermo/citología , Embrión no Mamífero , Endodermo/citología , Efrinas/genética , Efrinas/metabolismo , Mesodermo/citología , Receptores de la Familia Eph/genética , Receptores de la Familia Eph/metabolismo , Transducción de Señal , Proteínas de Xenopus/metabolismo , Xenopus laevis/genética , Xenopus laevis/metabolismoRESUMEN
Morphogenetic mechanisms such as cell movement or tissue separation depend on cell attachment and detachment processes, which involve adhesion receptors as well as the cortical cytoskeleton. The interplay between the two components is of stunning complexity. Most strikingly, the binding energy of adhesion molecules is usually too small for substantial cell-cell attachment, pointing to a main deficit in our present understanding of adhesion. In this Opinion article, I integrate recent findings and conceptual advances in the field into a coherent framework for cell adhesion. I argue that active cortical tension is best viewed as an integral part of adhesion, and propose on this basis a non-arbitrary measure of adhesion strength - the tissue surface tension of cell aggregates. This concept of adhesion integrates heterogeneous molecular inputs into a single mechanical property and simplifies the analysis of attachment-detachment processes. It draws attention to the enormous variation of adhesion strengths among tissues, whose origin and function is little understood.