Roles of cell adhesion molecules nectin and nectin-like molecule-5 in the regulation of cell movement and proliferation

In response to chemoattractants, migrating cells form protrusions, such as lamellipodia and filopodia, and structures, such as ruffles over lamellipodia, focal complexes and focal adhesions at leading edges. The formation of these leading edge structures is essential for directional cell movement. Nectin-like molecule-5 (Necl-5) interacts in cis with PDGF receptor and integrin alpha(v)beta(3), and enhances the activation of signalling molecules associated with these transmembrane proteins, which results in the formation of leading edge structures and enhancement of directional cell movement. When migrating cells come into contact with each other, cell-cell adhesion is initiated, resulting in reduced cell velocity. Necl-5 first interacts in trans with nectin-3. This interaction is transient and induces down-regulation of Necl-5 expression at the cell surface, resulting in reduced cell movement. Cell proliferation is also suppressed by the down-regulation of Necl-5, because the inhibitory effect of Necl-5 on Sprouty2, a negative regulator of the Ras signalling, is diminished. PDGF receptor and integrin alpha(v)beta(3), which have interacted with Necl-5, then form a complex with nectin, which initiates cell-cell adhesion and recruits cadherin to the nectin-based cell-cell adhesion sites to form stable adherens junctions. The formation of adherens junctions stops cell movement, in part through inactivation of integrin alpha(v)beta(3) caused by the trans-interaction of nectin. Thus, nectin and Necl-5 play key roles in the regulation of cell movement and proliferation.     

Cell adhesion and the immune system: a case study using earthworms

In the earthworm's immune system, cell adhesion, which occurs by putative receptors on leukocytes, is essential after recognition of self vs. non-self. Confrontation with foreign antigens is a normal event in the environment, replete with microbial pathogens that pose a threat to survival. To better understand what happens when an effector cell first recognizes a foreign target followed by its adhesion to it, isolated leukocytes, in sufficient quantities to be subjected to various analyses, have been extremely beneficial. In vitro approaches when accompanied by biochemical, immunological, and molecular technologies, have opened up new vistas concerning the immune response of earthworms and other invertebrates. The most recent discovery includes the preliminary identification of cell differentiation (CD) markers that play vital roles in recognitive and adhesive events. Certain leukocyte effectors show characteristics of natural killer (NK) cells that may act differently depending upon their source, whether autogeneic, allogeneic, xenogeneic, or expressed under normal or varying environmental conditions including exposure to xenobiotics. At the level of earthworm evolution, there is apparently a dissociation of phagocytosis from the process of killing by NK-like effectors. There are at least three future challenges. First, it is essential to determine the precise nature of the CD markers with respect to their molecular structure. Second, once their molecular and biochemical characteristics have been defined, the role of these markers in cellular and humoral mechanisms must be clarified in order to define effector cell products and resulting immune responses. Third, there is a need to differentiate between the several lytic factors that have been found in earthworms with respect to molecular structure, and biochemical and functional characterization.     

Mammary epithelial stem cells

It has recently been shown that the progeny from a single cell may comprise the epithelial population of a fully developed lactating mammary outgrowth in mice. Serial transplantation of epithelial fragments from this clonally derived gland demonstrates that the subsequently generated outgrowths are also comprised of progeny from the original antecedent. All epithelial cell types were found to be present within these clonal normal populations including luminal, myoepithelial, ductal, and lobule-committed epithelial progenitors and fully competent mammary epithelial stem cells. These observations demonstrate the presence of multipotent tissue-specific epithelial stem cells among the parenchyma of the murine mammary gland. Similarly, genetic analysis of contiguous portions of individual human mammary ducts within the same breast indicates their clonal derivation. Here, we discuss the properties, location, division-potential, senescence, and plasticity associated with mammary epithelial stem cells and present the developing evidence for their presence in human breast and their important role in the risk for breast cancer development. Further, we review the present morphologic and genetic evidence for the characterization of specific stem cell markers and lineage-limited progenitor cells in human and rodent mammary epithelium. Microsc. Res. Tech. 52:190-203, 2001. Published 2001 Wiley-Liss, Inc.     

Transcytosis of plasma macromolecules in endothelial cells: a cell biological survey

The modern exploration of endothelial cell biology is a largely interdisciplinary exercise. Cell biological, physiological, and more recently molecular biology approaches were used to study the pathways and the organelles involved in transcytosis of macromolecules in endothelial cell (EC). Here we discuss mainly the cell biological findings that revealed that EC have the attributes to fulfill the transport function. They are polarized cells, heterogeneous, and, thus, structurally and functionally adapted to the vascular bed in which they reside. The structural heterogeneity involves the number and distribution of plasmalemmal vesicles (caveolae), their generated channels, and the organization of intercellular junctions. The closely related functional heterogeneity comprises the degree of permeability for plasma molecules that vary as a function of organ. The EC are endowed with the cellular machinery to perform (1) endocytosis, that is to take up plasma proteins and the molecules they carry to be used for themselves (cholesterol-carrying low density lipoproteins, fatty acid carrying albumin, iron carrying transferrin, etc.), and (2) transcytosis, which implies to transport plasma proteins to the subjacent cells and tissues. The possible pathways for transport of molecules are transcellular, via caveolae and channels, and paracellular via intercellular junctions. Most of the results obtained, so far, indicate that transcytosis of albumin, low-density lipoproteins, metaloproteases, and insulin, is performed by cargo-vesicles and their generated channels. The paracellular pathway can be used for water and ions; in postcapillary venules, at the level of which approximately 30% of junctions are open to a space of 6 nm, small molecules may take this route. Recent data obtained by molecular biology techniques revealed that caveolae are endowed with the molecular machinery for fusion/fission, docking, and movement across cells. Moreover, the various and numerous molecules that have been detected in the caveolae membrane and the different functions assumed by this differentiated microdomain strengthen the postulate that there are at least two or more types of vesicles molecularly tailored for the local physiological requirements.     

Surface activity of cancer cells: The fusion of two cell aggregates

A key feature that distinguishes cancer cells from all other cells is their capability to spread throughout the body. Although how cancer cells collectively migrate by following molecular rules which influence the state of cell-cell adhesion contacts has been comprehensively formulated, the impact of physical interactions on cell spreading remains less understood. Cumulative effects of physical interactions exist as the interplay between various physical parameters such as (1) tissue surface tension, (2) viscoelasticity caused by collective cell migration, and (3) solid stress accumulated in the cell aggregate core region. This review aims to point out the role of these physical parameters in cancer cell spreading by considering and comparing the rearrangement of various mono-cultured cancer and epithelial model systems such as the fusion of two cell aggregates. While epithelial cells undergo volumetric cell rearrangement driven by the tissue surface tension, which directs cell movement from the surface to the core region of two-aggregate systems, cancer cells rather perform surface cell rearrangement. Cancer cells migrate toward the surface of the two-aggregate system driven by the solid stress while the surface tension is significantly reduced. The solid stress, accumulated in the core region of the two-aggregate system, is capable of suppressing the movement of epithelial cells that can undergo the jamming state transition; however, this stress enhances the movement of cancer cells. We have focused here on the multi-scale rheological modeling approaches that aimed at reproducing and understanding these biological systems.     

Structural changes and cell properties of human ovarian surface epithelium in ovarian pathophysiology

The surface epithelial cells of the ovary, which are modified peritoneal cells, form a single, focally pseudostratified layer. The Müllerian ducts differentiate after invagination of the coelomic mesothelium over the gonadal ridges during the 6th week of embryonic life. On the basis of the embryologically putative Müllerian potential of this epithelium, endometriosis can be explained by coelomic metaplasia from the peritoneum, including ovarian surface epithelium. Some pelvic endometriosis specimens have shown that epithelial cells on the ovary or pelvis are serially changed to endometriotic gland cells. Immunohistochemistry as well as scanning electron microscopy also reinforce the light-microscopical findings. A three-dimensional culture system demonstrated that human ovarian surface epithelial cells exhibited a glandular-stromal structure when they were cocultured with endometrial stromal cells in an estrogen-rich environment. Ovarian carcinomas in the epithelial-stromal category are thought to arise from the surface epithelium and its inclusions. The ovarian surface epithelium is physiologically involved in follicular rupture, oocyte release, and the subsequent repair of follicle wall during reproductive age. Simultaneously, ovulation may cause a loss of integrity of the surface epithelium, followed by accumulation of multiple mutations. The cortical invagination, surface stromal proliferation, and Müllerian differentiation of these cells are likely not to be an early step in the cancer development. However, the inclusion cysts are closely related with carcinogenesis because they are significantly more common in ovaries contralateral to those containing epithelial cancers than in control ovaries. As an in vitro study, ovarian carcinoma cell lines were established from simian virus 40 large T antigen-transformed human surface epithelial cells of the ovary. Further investigations of these cell lines may lead to insights into the preneoplastic and early stages of carcinomas. To clarify the pathogenesis of endometriosis and epithelial ovarian cancer, specifically designed studies of ovarian surface epithelium are required.     

Microfilaments and microtubules maintain endothelial integrity

The endothelium is a highly metabolic monolayer of cells regulating numerous physiological and pathological functions that maintain the permeability and thromboresistant functions of the endothelium. The structure and function of the endothelial cytoskeleton prevents vascular disease by regulating the structure of the endothelium to act as a resting molecular barrier to atherogenic proteins and by becoming an activated layer of migrating cells to repair denuding injuries. The purpose of this review is to examine the structure of the endothelial cytoskeleton and its roles in cell-cell and cell-substratum adhesion, cell signaling, and regulation of wound repair. Studies focused on the cellular and molecular biology of the structure and function of the endothelial cytoskeleton and in wound repair are reviewed. The cytoskeleton is a key regulator in maintaining endothelial integrity and in restoring integrity following injurious denudation, such as those that occur in the pathogenesis of atherosclerosis. Actin microfilaments and their associated adherens junctions and focal adhesions are important regulators of cell signaling, cell locomotion, cell adhesion, and wound repair mechanisms. Various proteins have been implicated in controlling cytoskeletal-based endothelial function and repair such as tyrosine kinases/phosphatases and the Rho family of proteins. The normal function of the endothelium is highly dependent on the endothelial cytoskeleton. Disruption and dysfunction of the cytoskeleton may result in impairment of endothelial function, subsequently tipping the balance towards vascular disease. Thus, an understanding of the cellular and molecular biology of the endothelial cytoskeleton is essential in our understanding of the pathogenesis of vascular disease, especially atherosclerosis.     

Organic anion transport across the choroid plexus

Several organic anion transport systems have recently been identified and localized at the apical and basolateral plasma membrane domains of choroid plexus epithelial cells. These organic anion transporters include (1) indirectly coupled Na(+)/dicarboxylate cotransport and dicarboxylate/organic anion exchange, which is represented on the molecular level by a member of the "kidney"-type organic anion transporter (OAT) family at the apical plasma membrane domain; (2) the organic anion transporting polypeptide 1 (Oatp1) and Oatp2, which both mediate typical "liver"-like organic anion transport activities at the apical and basolateral plasma membrane domains, respectively; and (3) the multidrug resistance protein Mrp1/MRP1 at the basolateral plasma membrane domain, and the P-glycoprotein Mdr1/MDR1 at an apical and subapical membrane vesicle compartment. This cellular transport polarity can account, at least in part, for the previously suggested physiologic transport properties of the choroid plexus epithelium and provides a framework for the identification and localization of additional organic anion transporters involved in the absorption and/or excretion of drugs and drug metabolites at the choroid plexus.     

Rodlet cells development in the intestine of sea bass (Dicentrarchus labrax)

The enigmatic rodlet cells (RCs) are characterized by conspicuous inclusions named “rodlets”. They were discovered over 100 years ago and were considered as parasites but shortly afterward interpreted as endogenous cells. The RCs have been described in different tissues of marine and freshwater teleosts, but their origin and function remain unknown. This work was designed to an ultrastructural study on RCs development and distribution in intestinal epithelium of Dicentrarchus labrax. Three different stages of RCs development from early precursor cells to mature phase were observed, as well as a migration and finally an extrusion of their contents. In this study, the immature cells were found near the basal epithelium membrane. They were mainly identified by a rough endoplasmic reticulum with dilated cisternae, by developing rodlets and a thin fibrillar coat. The maturing RCs, localized in the middle zone of the epithelium, appeared to be undergoing a reorganization of the cell organelles. The mature RCs, placed near the free surface, showed a thick subplasmalemmar fibrillar coat. Most of the organelles were aggregated at the cell apex with a basally located nucleus. A cellular polarity was more evident. One of the most conspicuous features was the occurrence of mature rodlets club‐sac in shape orientated toward the cell apex. Adhesive junctions between surface epithelial cells and RCs, while discharging their contents, were seen. We have connected morphological figures and distribution to different stages of development in RCs, supporting the hypothesis of their secretory function. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.     

Image processing techniques in a preliminary morphometric characterization of corneal epithelium by scanning electron microscopy

Several processing techniques of digital images allowed us to quantify the percentage of cell surface covered by microprojections (microvilli or microplicae) (SCM), the adhesion between epithelial cells by the parameter intercellular junctions (IJ), the size (cell area), shape (cell shape) and shade (cell shade) of cells on the corneal epithelium of nine rabbits. The data were analyzed and the epithelial cells were classified into three groups by cluster analysis. Assuming the representativeness of the sample, our findings suggest that for a normal corneal epithelium, 80% of the cells could show SCM >41%, and IJ >0.98 (being one a cell to cell junction without disruptions). Standard deviations of cell shade lower than 21 gray levels could indicate a tendency to lose the cell shade mosaic. Normal corneas could show a majority of cells (54–69%) included in group 2 with smaller mean size (80% of cells with cell area <242 μm²), higher SCM (80% of cells with SCM >44.83%), polygonal mean shape and brighter shade. Group 1 (15–30% of cells) could show a larger mean size (80% of cells with cell area >494 μm²), lower SCM (although 80% of cells with SCM >32.61%), circular mean shape and darker electron reflex. Group 3 could display a medium mean size, higher SCM (similar to group 2), circular mean shape (similar to group 1), and brighter shade. These analyses could possibly be used to further assess the corneal response to ocular drugs, contact lens, and surgical procedures or to discriminate between pathology stages. Microsc. Res. Tech. 73:1059–1066, 2010. © 2010 Wiley‐Liss, Inc.     

A novel method for a high enrichment of human corneal epithelial stem cells for genomic analysis

Understanding the molecular mechanisms that regulate the corneal epithelial stem cells (CESCs) in maintaining corneal homeostasis remains elusive largely due to the lack of a specific marker for their isolation. This study aims to enrich CESCs from human donor limbal epithelium and to evaluate the level of enrichment based on expression of ΔNp63α, a putative CESC marker. A two‐stage enrichment of CESCs was carried out. (a) The limbal basal epithelial cells were isolated by differential enzymatic treatment and five‐fold enrichment was achieved from 2% of CESCs present in the total limbal epithelium. The CESCs were quantified on the basis of two parameters—high expression of p63/ABCG2 and nucleus to cytoplasmic (N/C) ratio ≥0.7. (b) Cytospin smears of isolated basal cells were Giemsa stained and cells with N/C ratio ≥0.7 were separated by laser capture microdissection. This strategy resulted in an enrichment of CESCs to 78.57% based on two‐parameter analysis using p63 and 76.66% using ABCG2. RT‐PCR was carried out for ΔNp63 isoforms (α, β, and γ) and connexin‐43, with GAPDH for normalization. The expression of ΔNp63α was restricted to the enriched population of CESCs in contrast to its absence in limbal basal cells with N/C ratio <0.7 and CCECs. The unique expression of ΔNp63α and 5.9‐fold reduced connexin‐43 expression in the enriched population of CESCs indicates its high purity. Further analysis of these cells will help in elucidating the molecular mechanisms associated with stemness and also in identifying a specific marker for CESCs.     

质谱定量蛋白质组学技术筛选结直肠癌外周血单个核细胞差异表达蛋白

结直肠癌（CRC）是一种常见的、发生及发展过程复杂的消化系统癌症，其复杂、多级的发生发展过程会影响机体免疫功能，引起免疫变化。外周血单个核细胞（PBMC）是机体免疫系统的重要组成部分，且便于获取，是研究机体免疫功能的理想材料。本研究采用最新的数据非依赖采集（data independent acquision, DIA）质谱新方法结合Skyline软件对结直肠癌患者与良性肠病患者的PBMC蛋白进行定量比较，寻找差异表达蛋白，并对差异蛋白进行Reactome通路及GO分析。结果表明，共找到113个差异表达蛋白，其中，上调蛋白23个，下调蛋白90个，它们参与巨噬细胞、T细胞、树突细胞等多种外周免疫细胞的免疫活动。在这些差异蛋白中，上调蛋白Galectin-1及下调蛋白Dok-2和AHNAK1等蛋白与机体的免疫功能息息相关，有望成为外周血单个核细胞中的结直肠癌免疫标志物。     

Virus present in the reproductive tract of asymptomatic drones of honey bee (Apis mellifera l.), and possible infection of queen during mating

Virus particles and viral inclusions were detected by transmission electron microscopy examination of sections of the seminal vesicles and mucus gland of asymptomatic young drones from colonies of Apis mellifera lightly infested by Varroa mite. In the mucus gland the infection was found in the muscular sheath and epithelium, while in the seminal vesicle in cells of the outer serosa. Isolated viral particles were also observed in the hemolymph occupying the intercellular spaces of the muscular sheath fibers. In the muscle the virus appeared as polygonal crystalloid inclusions, while in the epithelium mainly inside cytoplasmic vesicles. The infected cells apparently are not damaged. The virus particles are present in the hemolymph and forming more mature structures, as crystalloids, in the muscle. This suggests that the virus is liberated in the body fluid and infects the tissues penetrating the cells through endocytosis. The presence of virus in mucus gland epithelial vesicles raise the possibility of its transference to the gland secretion and therefore, to the semen.     

Mechanisms of CSF secretion by the choroid plexus

The epithelial cells of the choroid plexus secrete cerebrospinal fluid (CSF), by a process that involves the movement of Na(+), Cl(-) and HCO(3)(-) from the blood to the ventricles of the brain. This creates the osmotic gradient, which drives the secretion of H(2)O. The unidirectional movement of the ions is achieved due to the polarity of the epithelium, i.e., the ion transport proteins in the blood-facing (basolateral) are different to those in the ventricular (apical) membranes. Saito and Wright (1983) proposed a model for secretion by the amphibian choroid plexus, in which secretion was dependent on activity of HCO(3)(-) channels in the apical membrane. The patch clamp method has now been used to study the ion channels expressed in rat choroid plexus. Two potassium channels have been observed that have a role in maintaining the membrane potential of the epithelial cell, and in regulating the transport of K(+) across the epithelium. An inward-rectifying anion channel has also been identified, which is closely related to ClC-2 channels, and has a significant HCO(3)(-) permeability. This channel is expressed in the apical membrane of the epithelium where it may play an important role in CSF secretion. A model of CSF secretion by the mammalian choroid plexus is proposed that accommodates these channels and other data on the expression of transport proteins in the choroid plexus.     

Mechanisms of cell-cell adhesion identified by immunofluorescent labelling with quantum dots: A scanning near-field optical microscopy approach

Scanning near-field optical microscopy (SNOM) has been employed to simultaneously acquire high-resolution fluorescence images along with shear-force atomic force microscopy from cell membranes. Implementing such a technique overcomes the limits of optical diffraction found in standard fluorescence microscopy and also yields vital topographic information. The application of the technique to investigate cell-cell adhesion has revealed the interactions of filopodia and their functional relationship in establishing adherens junctions. This has been achieved via the selective tagging of the cell adhesion protein, E-cadherin, by immunofluorescence labelling. Two labelling routes were explored; Alexa Fluor 488 and semiconductor quantum dots. The quantum dots demonstrated significantly enhanced photostability and high quantum yield making them a versatile alternative to the conventional organic fluorophores often used in such a study. Analysis of individual cells revealed that E-cadherin is predominantly located along the cell periphery but is also found to extend throughout their filopodia. We have demonstrated that with a fully optimised sample preparation methodology, quantum dot labelling in conjunction with SNOM imaging can be successfully applied to interrogate biomolecular localisation within delicate cellular membranes.     

Surface ultrastructure of the gill filaments and the secondary lamellae of the catfish, Rita rita, and the carp, Cirrhinus mrigala

Surface ultrastructures of gill filaments and secondary lamellae of Rita rita and Cirrhinus mrigala, inhabiting different ecological habitat, were investigated to unravel adaptive modifications. R. rita is a sluggish, bottom dwelling carnivorous catfish, which inhabits regions of river with accumulations of dirty water. It retains its viability for long time if taken out of water. C. mrigala is an active bottom dwelling Indian major carp, which lives in relatively clean water and dies shortly after taken out of water. In R. rita, gill septa between gill filaments are reduced. Microridges on epithelial cells covering gill filaments are often continuous and arranged concentrically. Secondary lamellae are extensive. The epithelium appears corrugated, show irregular elevations and shallow depressions, and microridges on epithelial cells appear fragmented. In C. mrigala, in contrast, the gill septa are extensive. Microridges on epithelial cells covering gill filaments are fragmented. Secondary lamellae are less extensive. The epithelium appears smooth and microridges on epithelial cells are relatively inconspicuous. These differences have been considered adaptive modification in relation to habit and ecological niches inhabited by two fish species. Presence of mucous goblet cells on gill filaments is discussed in relation to their functions including precipitation of the sediments and preventing clogging of gill filaments. Infrequent mucous goblet cells in the epithelium of secondary lamellae in two fish species are considered an adaptation, minimizing thickness of the epithelium to reduce barrier between blood and water for favoring gasses exchange with increased efficiency.     

Adrenomedullin functions as an important tumor survival factor in human carcinogenesis

Adrenomedullin (AM) is a pluripotent regulatory peptide initially isolated from a human pheochromocytoma (adrenal tumor) and subsequently shown to play a critical role in cancer cell division, tumor neovascularization, and circumvention of programmed cell death, thus it is an important tumor cell survival factor underlying human carcinogenesis. A variety of neural and epithelial cancers have been shown to produce abundant amounts of AM. Recent findings have implicated elevation of serum AM with the onset of malignant expression. In addition, patients with tumors producing high levels of this peptide have a poor prognostic clinical outcome. Given that most human epithelial cancers display a microenvironment of reduced oxygen tension, it is interesting to note that AM and several of its receptors are upregulated during hypoxic insult. The existence of such a regulatory pathway has been implicated as the basis for the overexpression of AM/AM-R in human malignancies, thereby generating a subsequent autocrine/paracrine growth advantage for the tumor cell. Furthermore, AM has been implicated as a potential immune suppressor substance, inhibiting macrophage function and acting as a newly identified negative regulator of the complement cascade, protective properties which may help cancer cells to circumvent immune surveillance. Hence, AM's traditional participation in normal physiology (cited elsewhere in this issue) can be extended to a primary player in human carcinogenesis and may have clinical relevance as a biological target for the intervention of tumor progression.     

Extrusion of colonic epithelial cells in vitro

Rat colonic mucosae fixed in situ in Ussing chambers provided a model of the extrusion of absorptive enterocytes and less commonly of goblet and enteroendocrine cells. The cells were lost at extrusion zones midway between crypt mouths. Even in mucosae in which the number of extruding cells was large, epithelial continuity was maintained as evaluated morphologically and electrophysiologically. Beneath points of remaining contact between desquamating cells and the epithelial sheet, microfilaments of the terminal web formed band-like structures linking adjacent junctional complexes. Freeze-fracture replicas disclosed extensive macular regions of tight junction strands in the plasma membranes of desquamating cells. Tight junctions between newly neighboring cells were often irregular and often occurred beneath the terminal web region. Dithio-threitol enhanced cell loss and increased basal epithelial conductance, but histological continuity was maintained and the mucosae continued to respond typically to bradykinin. These observations suggest that during the loss of senescent enterocytes, tight junctions are maintained; old junctional elements are lost, and tight junctions are formed between remaining adjacent cells. This model offers a means to study the synthesis and turnover of tight junctions and the maintenance of the colonic epithelial barrier.     

In vitro confocal imaging of the rabbit cornea

We were able to observe in vitro the fine structure of the rabbit cornea using a laser scanning confocal microscope, especially in the regions between Descemet's membrane and the epithelial basal lamina. We observed submicrometre filaments throughout the stroma with high concentrations adjacent to Descemet's membrane, and found extensive interconnecting processes between stromal keratocytes. There are numerous regions containing nerve plexuses in the stroma. We found a deeply convoluted basal lamina adjacent to the epithelium, and observed regions containing junctions between endothelial cells in fluorescent images of rabbit corneas stained with the actin-specific compound fluorescein phalloidin.     

Dynamic control of reversible cell adhesion and actin cytoskeleton in the mouth of Beroë

Cell-cell adhesion in the various types of intercellular junctions of differentiated tissues is relatively stable and permanent. In migrating cells of embryos, or in wound closure, inflammatory responses and tumors of adult tissues, however, bonds between cells are made and broken and made again, i.e., cell-cell adhesions are transient and reversible. These nonjunctional contacts lack the organized structure of intercellular junctions, but may initiate their tissue-specific formation during development. Investigation of dynamic, nonjunctional cell-cell adhesions has been hampered by the asynchronous and heterogeneous distribution of these transient contacts among groups of moving cells. We recently discovered a novel system of reversible cell adhesion in a differentiated tissue that overcomes this difficulty. Here I review our current knowledge of this system, particularly its unique experimental advantages for investigating the mechanisms and control of dynamic cell adhesion.