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Integrin-mediated cell adhesion regulates a vast number of biological processes including migration, survival and proliferation of cells. It is therefore not surprising that defects in integrin function are often rate-limiting for development and profoundly affect the progression of several diseases. The functions of integrins are mediated through the recruitment of cytoplasmic plaque proteins. One of these is integrin-linked kinase, which connects integrins to the actin cytoskeleton and transduces signals through integrins to the extracellular matrix and from integrins to various subcellular compartments. [Copyright &y& Elsevier]

Perlecan is a highly conserved heparan sulfate proteoglycan in cartilage and basement membranes. We identified chick perlecan and a 90 KD perlecan fragment in vivo using a newly generated monoclonal antibody. Chick perlecan is, like its human and mouse homologue, a hybrid heparan sulfate/chondroitin sulfate proteoglycan with a core protein of 400 KD. Analysis of the 90 KD fragment by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and Capillary LC nano Electrospray Ionization tandem MS (LC nano ESI MS/MS) showed that it belonged to domain IV of the perlecan core protein. We found that full-length perlecan and its domain IV fragment are abundant in embryonic vitreous body and serum. Their expression in vitreous and serum is greatly down-regulated shortly after hatching of the chick. We speculate that the abundance of perlecan in the embryonic circulation and vitreous reflects the ongoing formation of new BMs in the expanding vascular system and the growing retina. In addition, we found that perlecan as a substrate does not support, rather inhibits neurite outgrowth. [Copyright &y& Elsevier]

In this paper, we propose an ontogeny for previously identified cells from the median domain in the midline of the embryonic brain of the grasshopper Schistocerca gregaria. The so-called lateral cells (LCs) are characteristically located laterally within the median domain at its border with the protocerebral hemispheres. The LC occurs singly and can be identified in the early embryo on the basis of their expression of the cell surface lipocalin Lazarillo. Using immunocytochemical, dye injection, electron microscopical and histological methods, we show that these LC are neurons and derive as postmitotic cells directly from the epithelium of the median domain. Further, they and the other identified cells of the median domain such as the protocerebral commissure pioneers (PCP), co-express the Mes-3 antigen, consistent with a derivation from the mesectodermal germ layer of the embryo. Subsequent to axogenesis, electron microscopy reveals that these Mes-3-expressing LC fasciculate with the co-expressing PCPs within the developing protocerebral commissure. We present a model for the origin of all these cells based on histological data and bromodeoxyuridine incorporation. The model suggests a delamination of cells from the mesectoderm followed by a migration to their ultimate sites within the median domain. [Copyright &y& Elsevier]

Our understanding of MMP expression during corneal repair has previously relied upon animal models, isolated human biopsy specimens and cell culture studies. The aim of this study was to determine the temporal and spatial expression of matrix metalloproteinases following wounding of cultured human corneal tissue. Human corneas were cultured and cut into six pieces. The epithelium was removed with a corneal brush. The tissue was then re-cultured and tissue pieces were fixed up to 7 days post-wounding. Matrix metalloproteinases were detected by in situ hybridisation and immunohistochemistry. Intracellular laminin-5, a marker of migratory epithelial cells, was located immunohistologically. In the time scale studied tissue series from nine corneas achieved coverage of the stroma with epithelial cells and partial repair of damaged basement membrane, demonstrated by the Periodic acid-Schiff reaction and haematoxylin and eosin counter-staining. By day 3, migrating epithelial cells and stromal cells beneath the wounded area expressed collagenase-1 (MMP-1). Stromelysin-1 (MMP-3) was expressed only by fibroblast-like stromal cells. Stromelysin-2 (MMP-10) was detected in migrating epithelial cells and remained when the stroma was surrounded by a monolayer of epithelial cells. By day 7, development of multi-layered epithelium around the tissue coincided with cessation of MMP expression in both epithelial and stromal cells, except for MMP-9, which remained in epithelial basal cells. Tissue inhibitor of matrix metalloproteinase-1 was mainly associated with stromal cells and was reduced upon formation of a multi-layered epithelium. This study demonstrates matrix metalloproteinase expression in epithelial and fibroblast-like cells following wounding of human corneal tissue in culture where the cells remain in contact with their natural matrices. [Copyright &y& Elsevier]

Generation of double knockout mice for collagen types XV and XVIII indicated surprisingly that the mice are viable and do not suffer from any new major defects. Although the two collagens are closely related molecules sharing similarities in tissue expression, we conclude that their biological roles are essentially separate, that of type XV in muscle and type XVIII in the eye. Detailed comparisons of the null mice eyes indicated that type XV collagen seems to be involved in the tunica vasculosa lentis regression process, whereas type XVIII is in the regression of vasa hyaloidea propria, and only minor compensatory effects could be detected. Furthermore, the essential role of type XVIII collagen in the eye is highlighted by the occurrence of this collagen in the epithelial basement membranes of the iris and the ciliary body and in the inner limiting membrane of the retina, sites lacking type XV. [Copyright &y& Elsevier]

Dystroglycan (DG) forms part of a cell surface laminin receptor complex and is believed to play a critical role in the assembly and homeostasis of basement membranes (BM). The receptor complex is made up of α- and β-DG subunits and is found in muscle, epithelial and nerve tissue. In the cochlea, DG may be involved in the abnormal accumulation of laminin seen in the thickened BM of strial capillaries with age. This excess deposition of laminin is thought to lead to capillary necrosis and contribute to degeneration of the stria vascularis (SV). Here we assessed the presence and distribution of DG in the developing, mature and senescent gerbil cochlea in order to ascertain whether altered patterns of expression are a factor in age-related pathology. Western blots of proteins isolated from the entire cochlea demonstrated the presence of the α-DG subunit. mRNA encoding DG was identified in microdissected specimens of the lateral wall and the combined organ of Corti/modiolus by RT-PCR analysis. Immunohistochemical experiments localized α-DG in epithelial BMs and regions of epithelial cell–cell contact with no intervening BM in the developing and mature cochlea. Immunoreactive α-DG was present in the BM underlying strial capillaries and in vessels of the central portion of the auditory nerve, but was not detected in any other vessels in the cochlea. Age-related changes in α-DG expression were observed only in the SV where a marked decrease in α-DG immunoreactivity was seen in the BM of strial capillaries as well as throughout the SV. The results demonstrate the selective expression of α-DG in both BM and non-BM sites in the mature cochlea and suggests its involvement in both developmental and aging processes. [Copyright &y& Elsevier]

Status of tumor progression (either remaining in situ, or becoming invasive/metastatic) may be defined largely by subtle interactions (‘cross-talk’) in a microenvironment formed by interfacing tumor cell and host cell membrane domains (termed ‘glycosynapses’) involved in glycosylation-dependent cell adhesion and signaling. Functional roles of tumor-associated gangliosides, organized in glycosynapses of three types of tumor cell lines, are discussed. Gangliosides function as adhesion receptors or as ‘sensors’ that can be stimulated by antibodies, with consequent activation of signal transducers leading to enhanced motility and invasiveness. [Copyright &y& Elsevier]

Lack of type XV collagen in mice results in mild skeletal myopathy and increases vulnerability to exercise-induced skeletal muscle and cardiac injury [Proc. Natl. Acad. Sci. USA 98 (2001), 1194]. The expression of type XV collagen was studied during murine fetal development from 10.5 to 18.5 dpc using immunofluorescence. The first sign of type expression was seen in the capillaries of many tissues at 10.5 dpc, some of them showing developmental transitions in the expression. Interestingly, capillaries forming the blood–brain barrier and those of the sinusoidal type were essentially lacking in this collagen. Early expression was also detected in the skeletal muscle and peripheral nerves, while expression in the heart, kidney and lung appeared to be developmentally regulated. In addition, distinct staining was found in the perichondrium of the cartilage. Collectively, the dynamics of its expression during development, its localization in the basement membrane — fibrillar matrix interface and the consequences of its absence in mice suggest a structural role in providing stability at least in skeletal muscle and capillaries. The early prominent expression of type XV collagen in newly forming blood vessels could also indicate a possible role in angiogenic processes. [Copyright &y& Elsevier]

The interaction of extracellular matrix and receptors plays a role in tissue homeostasis. The thickened strial capillary basement membrane (SCBM) reported in animal models of presbycusis and Alport’s syndrome might be secondary to elevated synthesis and/or decreased turnover of specific basement membrane (BM) components. In this study, expression of specific BM proteins, integrin receptors and mediators of matrix turnover in the murine lateral wall were determined using cDNA probes and antibodies. The presence of collagen α1 and α2(IV) and laminin-8 in the SCBM was verified. The integrin subunits α3, αv and β1, cell surface receptors for the BM proteins, localized primarily to the SCBM and/or the strial marginal cells as did TIMP-3, a tissue inhibitor of matrix metalloproteinase. The epithelial cell line SV-k1, derived from the lateral wall of the ‘immortomouse’, showed expression of the same BM proteins as well as demonstrating the presence of markers specific to strial marginal cells, namely Na,K-ATPase α1 and β2 subunits. Thus, the cultured cells are identified as deriving from marginal cells of the stria vascularis. Moreover, these data suggest that a culture system using this marginal cell line will be useful to delineate mechanisms underlying the pathologic accumulation of extracellular matrix in the SCBM. [Copyright &y& Elsevier]

Increased and changed deposition of extracellular matrix proteins is a key feature of airway wall remodeling in obstructive pulmonary diseases, including asthma and chronic obstructive pulmonary disease. Studies have highlighted that the deposition of various basement membrane proteins in the lung tissue is altered and that these changes reflect tissue compartment specificity. Inflammatory responses in both diseases may result in the deregulation of production and degradation of these proteins. In addition to their role in tissue development and integrity, emerging evidence indicates that basement membrane proteins also actively modulate cellular processes in obstructive airway diseases, contributing to disease development, progression and maintenance. In this review, we summarize the changes in basement membrane composition in airway remodeling in obstructive airway diseases and explore their potential application as innovative targets for treatment development., (© 2021 The Author(s).)

The diverse populations of tissue-resident and transitory T cells present in the skin share a common functional need to enter, traverse, and interact with their environment. These processes are largely dependent on the regulated expression of adhesion molecules, such as selectins and integrins, which mediate bidirectional interactions between immune cells and skin stroma. Dysregulation and engagement of adhesion pathways contribute to ectopic T-cell activity in tissues, leading to the initiation and/or exacerbation of chronic inflammation. In this paper, we review how the molecular interactions supported by adhesion pathways contribute to T-cell dynamics and function in the skin. A comprehensive understanding of the molecular mechanisms underpinning T-cell adhesion in inflammatory skin disorders will facilitate the development of novel tissue-specific therapeutic strategies., (© 2021 The Authors.)

Type XV collagen is a non-fibrillar collagen that is associated with basement membranes and belongs to the multiplexin subset of the collagen superfamily. Collagen XV was initially studied because of its sequence homology with collagen XVIII/endostatin whose anti-angiogenic and anti-tumorigenic properties were subjects of wide interest in the past years. But during the last fifteen years, collagen XV has gained growing attention with increasing number of studies that have attributed new functions to this widely distributed collagen/proteoglycan hybrid molecule. Despite the cumulative evidence of its functional pleiotropy and its evolutionary conserved function, no review compiling the current state of the art about collagen XV is currently available. Here, we thus provide the first comprehensive view of the knowledge gathered so far on the molecular structure, tissue distribution and functions of collagen XV in development, tissue homeostasis and disease with an evolutionary perspective. We hope that our review will open new roads for promising research on collagen XV in the coming years., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Introduction: The basement membrane (BM) is a sheet-like extracellular matrix (ECM) lining the basal side of epithelial and endothelial cells. The molecular composition of the BM diversifies as embryonic development proceeds, providing optimized microenvironments for individual cell types. In post-implantation stage embryos, the embryonic BMs are essential for differentiation of the epiblast, a layer of multipotent embryonic stem cells, and subsequent embryogenesis. To better understand the role of BMs and cell-BM interactions in early embryogenesis, it is imperative to accumulate information on the molecular entities of the embryonic BMs., Methods: We analyzed the expressions and localizations of 20 major BM proteins (11 laminin subunits, 6 type IV collagen subunits, nidogen-1 and -2, and perlecan) and other ECM-related proteins such as fibronectin and integrins in post-implantation stage embryos by immunohistochemistry., Results: We found that a set of BM proteins, laminin α5, β1, and γ1 (comprising laminin-511), type IV collagen α1 and α2 (yielding type IV collagen α1 2 α2 [IV]), nidogen-1 and -2, and perlecan, were consistently present in the epiblast/ectoderm BMs throughout the early post-implantation stages. In contrast, laminin α1 was detected in the epiblast BM at E5.5 but decreased in later stages, suggesting that laminin-511 is a major laminin isoform in the early embryonic BM. In addition, fibronectin, a mesenchymal ECM protein, was enriched in the endoderm BM, indicating that the BM compositions differ between the ectoderm and the endoderm. Consistent with these observations, integrin α5, a high-affinity receptor for fibronectin, was localized in the endoderm, while integrin α6, a receptor for laminin-511, was localized in the ectoderm., Conclusions: The embryonic BMs underlying the epiblast/ectoderm contain a common toolkit comprising laminin-511, type IV collagen (α1 2 α2 [IV]), nidogen-1 and -2, and perlecan, providing a physiological basis for the utility of laminin-511 as a culture substrate for pluripotent stem cells. The distinctive association of laminin-511 and fibronectin with endodermal and ectodermal cells, together with the differential expression of integrin α5 and α6 in these cells, suggests that the ectodermal and endodermal cells rely on their integrin-dependent interactions with laminin-511 and fibronectin, respectively, to ensure their fate specification in embryonic development., (© 2019 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

SLUG, a member of the SNAIL family of transcriptional repressors, is known to play a diverse number of roles in the cell, and its deregulation has been observed in a variety of cancers including breast. Here, we focus on SLUG's role as a master regulator of mammary epithelial cell (MEC) fate and lineage commitment in the normal mammary gland, and discuss how aberrant SLUG expression can influence breast tumor formation, phenotype, and progression. Specifically, we discuss SLUG's involvement in MEC differentiation, stemness, cellular plasticity, and the epithelial to mesenchymal transition (EMT), and highlight the complex connection between these programs during development and disease progression. Undoubtedly, delineating how molecular factors influence lineage identity and cell-state dynamics in the normal mammary gland will contribute to our understanding of breast tumor heterogeneity.