Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.Cell-Matrix Junctions: Specialized areas at the CELL MEMBRANE where a cell attaches to the EXTRACELLULAR MATRIX or other substratum.Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Cell Adhesion: Adherence of cells to surfaces or to other cells.Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of CONNEXINS, the family of proteins which form the junctions.Intercellular Junctions: Direct contact of a cell with a neighboring cell. Most such junctions are too small to be resolved by light microscopy, but they can be visualized by conventional or freeze-fracture electron microscopy, both of which show that the interacting CELL MEMBRANE and often the underlying CYTOPLASM and the intervening EXTRACELLULAR SPACE are highly specialized in these regions. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p792)Tight Junctions: Cell-cell junctions that seal adjacent epithelial cells together, preventing the passage of most dissolved molecules from one side of the epithelial sheet to the other. (Alberts et al., Molecular Biology of the Cell, 2nd ed, p22)Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Adherens Junctions: Anchoring points where the CYTOSKELETON of neighboring cells are connected to each other. They are composed of specialized areas of the plasma membrane where bundles of the ACTIN CYTOSKELETON attach to the membrane through the transmembrane linkers, CADHERINS, which in turn attach through their extracellular domains to cadherins in the neighboring cell membranes. In sheets of cells, they form into adhesion belts (zonula adherens) that go all the way around a cell.Neuromuscular Junction: The synapse between a neuron and a muscle.Matrix Metalloproteinase 2: A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.Matrix Metalloproteinases: A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.Nuclear Matrix: The residual framework structure of the CELL NUCLEUS that maintains many of the overall architectural features of the cell nucleus including the nuclear lamina with NUCLEAR PORE complex structures, residual CELL NUCLEOLI and an extensive fibrogranular structure in the nuclear interior. (Advan. Enzyme Regul. 2002; 42:39-52)Connexins: A group of homologous proteins which form the intermembrane channels of GAP JUNCTIONS. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions.Connexin 43: A 43-kDa peptide which is a member of the connexin family of gap junction proteins. Connexin 43 is a product of a gene in the alpha class of connexin genes (the alpha-1 gene). It was first isolated from mammalian heart, but is widespread in the body including the brain.Bone Matrix: Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.Matrix Metalloproteinase Inhibitors: Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES.Matrix Metalloproteinase 1: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving FIBRILLAR COLLAGEN. It can degrade interstitial collagens, types I, II and III.Zonula Occludens-1 Protein: A 195-kDa zonula occludens protein that is distinguished by the presence of a ZU5 domain at the C-terminal of the molecule.Esophagogastric Junction: The area covering the terminal portion of ESOPHAGUS and the beginning of STOMACH at the cardiac orifice.Occludin: A MARVEL domain protein that plays an important role in the formation and regulation of the TIGHT JUNCTION paracellular permeability barrier.Matrix Metalloproteinase 3: An extracellular endopeptidase of vertebrate tissues similar to MATRIX METALLOPROTEINASE 1. It digests PROTEOGLYCAN; FIBRONECTIN; COLLAGEN types III, IV, V, and IX, and activates procollagenase. (Enzyme Nomenclature, 1992)Tight Junction Proteins: Proteins that take part in the formation or structure of TIGHT JUNCTIONS.Holliday Junction Resolvases: Enzymes that recognize CRUCIFORM DNA structures and introduce paired incisions that help to resolve the structure into two DNA helices.Freeze Fracturing: Preparation for electron microscopy of minute replicas of exposed surfaces of the cell which have been ruptured in the frozen state. The specimen is frozen, then cleaved under high vacuum at the same temperature. The exposed surface is shadowed with carbon and platinum and coated with carbon to obtain a carbon replica.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Cadherins: Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.Matrix Metalloproteinase 14: A transmembrane domain-containing matrix metalloproteinase. It is synthesized as an inactive zymogen that is activated by the action of PROPROTEIN CONVERTASES such as FURIN. Matrix metalloproteinase 14 plays a direct role in the cleavage of proteins in the pericellular environment. In addition, it can function indirectly by enzymatically activating the proprotein form of MATRIX METALLOPROTEINASE 15.Matrix Metalloproteinase 7: The smallest member of the MATRIX METALLOPROTEINASES. It plays a role in tumor progression.Matrix Metalloproteinase 13: A secreted matrix metalloproteinase that plays a physiological role in the degradation of extracellular matrix found in skeletal tissues. It is synthesized as an inactive precursor that is activated by the proteolytic cleavage of its N-terminal propeptide.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.DNA, Cruciform: A cross-shaped DNA structure that can be observed under the electron microscope. It is formed by the incomplete exchange of strands between two double-stranded helices or by complementary INVERTED REPEAT SEQUENCES that refold into hairpin loops on opposite strands across from each other.Claudin-1: An integral membrane protein that is localized to TIGHT JUNCTIONS, where it plays a role in controlling the paracellular permeability of polarized cells. Mutations in the gene for claudin-1 are associated with Neonatal Ichthyosis-Sclerosing Cholangitis (NISCH) Syndrome.Matrix Metalloproteinases, Membrane-Associated: Matrix metalloproteinases that are associated with the CELL MEMBRANE, either through transmembrane domains or GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORS. Membrane-type matrix metalloproteinases may act within the pericellular environment to influence the process of CELL MIGRATION.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.Matrix Metalloproteinase 12: A secreted matrix metalloproteinase which is highly expressed by MACROPHAGES where it may play a role in INFLAMMATION and WOUND HEALING.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Tissue Inhibitor of Metalloproteinase-1: A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a N-glycosylated protein, molecular weight 28 kD, produced by a vast range of cell types and found in a variety of tissues and body fluids. It has been shown to suppress metastasis and inhibit tumor invasion in vitro.Desmosomes: A type of junction that attaches one cell to its neighbor. One of a number of differentiated regions which occur, for example, where the cytoplasmic membranes of adjacent epithelial cells are closely apposed. It consists of a circular region of each membrane together with associated intracellular microfilaments and an intercellular material which may include, for example, mucopolysaccharides. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990; Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Matrix Metalloproteinases, Secreted: A subclass of matrix metalloproteinases that are secreted into the pericellular space.Viral Matrix Proteins: Proteins associated with the inner surface of the lipid bilayer of the viral envelope. These proteins have been implicated in control of viral transcription and may possibly serve as the "glue" that binds the nucleocapsid to the appropriate membrane site during viral budding from the host cell.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Tissue Inhibitor of Metalloproteinases: A family of secreted protease inhibitory proteins that regulates the activity of SECRETED MATRIX METALLOENDOPEPTIDASES. They play an important role in modulating the proteolysis of EXTRACELLULAR MATRIX, most notably during tissue remodeling and inflammatory processes.Zonula Occludens-2 Protein: A zonula occludens protein subtype found in epithelial cell junctions. Several isoforms of zonula occludens-2 protein exist due to use of alternative promoter regions and alternative mRNA splicings.Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Epithelium: One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.Neuromuscular Junction Diseases: Conditions characterized by impaired transmission of impulses at the NEUROMUSCULAR JUNCTION. This may result from disorders that affect receptor function, pre- or postsynaptic membrane function, or ACETYLCHOLINESTERASE activity. The majority of diseases in this category are associated with autoimmune, toxic, or inherited conditions.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Tissue Inhibitor of Metalloproteinase-2: A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a 21-kDa nonglycosylated protein found in tissue fluid and is secreted as a complex with progelatinase A by human fibroblast and uncomplexed from alveolar macrophages. An overexpression of TIMP-2 has been shown to inhibit invasive and metastatic activity of tumor cells and decrease tumor growth in vivo.Glycyrrhetinic Acid: An oleanolic acid from GLYCYRRHIZA that has some antiallergic, antibacterial, and antiviral properties. It is used topically for allergic or infectious skin inflammation and orally for its aldosterone effects in electrolyte regulation.Carbenoxolone: An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Proteoglycans: Glycoproteins which have a very high polysaccharide content.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.PhosphoproteinsBlotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.alpha Catenin: A catenin that binds F-ACTIN and links the CYTOSKELETON with BETA CATENIN and GAMMA CATENIN.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.Gelatinases: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-.Heptanol: A colorless liquid with a fragrant odor. It is used as an intermediate, solvent and in cosmetics.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Matrix Metalloproteinase 10: A secreted matrix metalloproteinase that may play a role in matrix degradation during WOUND HEALING. It is expressed at high levels by KERATINOCYTES, suggesting its role in keratinocyte migration.Electric Impedance: The resistance to the flow of either alternating or direct electrical current.Desmoplakins: Desmoplakins are cytoskeletal linker proteins that anchor INTERMEDIATE FILAMENTS to the PLASMA MEMBRANE at DESMOSOMES.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Microscopy, Electron, Scanning: Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY.Claudin-3: A ubiquitously-expressed claudin subtype that acts as a general barrier-forming protein in TIGHT JUNCTIONS. Elevated expression of claudin-3 is found in a variety of tumor cell types, suggesting its role as a therapeutic target for specific ANTINEOPLASTIC AGENTS.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Motor Endplate: The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors.Cartilage Oligomeric Matrix Protein: Major component of chondrocyte EXTRACELLULAR MATRIX of various tissues including bone, tendon, ligament, SYNOVIUM and blood vessels. It binds MATRILIN PROTEINS and is associated with development of cartilage and bone.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Basement Membrane: A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers.Integrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Claudin-4: A claudin subtype that takes part in maintaining the barrier-forming property of TIGHT JUNCTIONS. Claudin-4 is found associated with CLAUDIN-8 in the KIDNEY COLLECTING DUCT where it may play a role in paracellular chloride ion reabsorption.Cartilage: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.Collagen Type I: The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Catenins: A family of cytoskeletal proteins that play essential roles in CELL ADHESION at ADHERENS JUNCTIONS by linking CADHERINS to the ACTIN FILAMENTS of the CYTOSKELETON.Mice, Inbred C57BLTransfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Receptors, Cholinergic: Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Tenascin: Hexameric extracellular matrix glycoprotein transiently expressed in many developing organs and often re-expressed in tumors. It is present in the central and peripheral nervous systems as well as in smooth muscle and tendons. (From Kreis & Vale, Guidebook to the Extracellular Matrix and Adhesion Proteins, 1993, p93)Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Junctional Adhesion Molecules: A family of membrane glycoproteins localized to TIGHT JUNCTIONS that contain two extracellular Ig-like domains, a single transmembrane segment, and a cytoplasmic tail of variable length.beta Catenin: A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Microscopy, Immunoelectron: Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Calcification, Physiologic: Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cartilage, Articular: A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact.Matrix Metalloproteinase 11: A secreted matrix metalloproteinase that is believed to play a role in EXTRACELLULAR MATRIX remodeling and cell fate determination during normal and pathological processes. Matrix metalloproteinase 11 was originally isolated in primary BREAST NEOPLASMS and may be involved in the process of tumorigenesis.Octanols: Isomeric forms and derivatives of octanol (C8H17OH).Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Chondrocytes: Polymorphic cells that form cartilage.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Wound Healing: Restoration of integrity to traumatized tissue.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Tissue Engineering: Generating tissue in vitro for clinical applications, such as replacing wounded tissues or impaired organs. The use of TISSUE SCAFFOLDING enables the generation of complex multi-layered tissues and tissue structures.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Position-Specific Scoring Matrices: Tabular numerical representations of sequence motifs displaying their variability as likelihood values for each possible residue at each position in a sequence. Position-specific scoring matrices (PSSMs) are calculated from position frequency matrices.Rana pipiens: A highly variable species of the family Ranidae in Canada, the United States and Central America. It is the most widely used Anuran in biomedical research.Stress, Mechanical: A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.Cell Line, Tumor: A cell line derived from cultured tumor cells.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Matrilin Proteins: PROTEOGLYCANS-associated proteins that are major components of EXTRACELLULAR MATRIX of various tissues including CARTILAGE; and INTERVERTEBRAL DISC structures. They bind COLLAGEN fibers and contain protein domains that enable oligomer formation and interaction with other extracellular matrix proteins such as CARTILAGE OLIGOMERIC MATRIX PROTEIN.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Cell Culture Techniques: Methods for maintaining or growing CELLS in vitro.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.gamma Catenin: A multi-functional catenin that is highly homologous to BETA CATENIN. Gamma catenin binds CADHERINS and helps link their cytoplasmic tails to ACTIN in the CYTOSKELETON via ALPHA CATENIN. It is also found in DESMOSOMES where it mediates the link between DESMOSOMAL CADHERINS and DESMOPLAKIN.Hyaluronic Acid: A natural high-viscosity mucopolysaccharide with alternating beta (1-3) glucuronide and beta (1-4) glucosaminidic bonds. It is found in the UMBILICAL CORD, in VITREOUS BODY and in SYNOVIAL FLUID. A high urinary level is found in PROGERIA.Kinetics: The rate dynamics in chemical or physical systems.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or N-acetylgalactosamine.Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.Caco-2 Cells: Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Morphogenesis: The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.Gelatin: A product formed from skin, white connective tissue, or bone COLLAGEN. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories.Vinculin: A cytoskeletal protein associated with cell-cell and cell-matrix interactions. The amino acid sequence of human vinculin has been determined. The protein consists of 1066 amino acid residues and its gene has been assigned to chromosome 10.Chick Embryo: The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).MARVEL Domain Containing 2 Protein: A tight junction-associated MARVEL protein that may play a role in separating the endolymphatic and perilymphatic spaces of the ORGAN OF CORTI. Defects in the gene that codes for MARVELD2 protein are a cause of deafness autosomal recessive type 49.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.Microfilament Proteins: Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.Matrix Attachment Regions: Regions of the CHROMATIN or DNA that bind to the NUCLEAR MATRIX. They are found in INTERGENIC DNA, especially flanking the 5' ends of genes or clusters of genes. Many of the regions that have been isolated contain a bipartite sequence motif called the MAR/SAR recognition signature sequence that binds to MATRIX ATTACHMENT REGION BINDING PROTEINS.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Agrin: A protein component of the synaptic basal lamina. It has been shown to induce clustering of acetylcholine receptors on the surface of muscle fibers and other synaptic molecules in both synapse regeneration and development.Antigens, CD29: Integrin beta-1 chains which are expressed as heterodimers that are noncovalently associated with specific alpha-chains of the CD49 family (CD49a-f). CD29 is expressed on resting and activated leukocytes and is a marker for all of the very late activation antigens on cells. (from: Barclay et al., The Leukocyte Antigen FactsBook, 1993, p164)Zonula Occludens Proteins: A family of proteins that play a role in TIGHT JUNCTION formation by binding to and anchoring proteins to the ACTIN CYTOSKELETON.Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Lens, Crystalline: A transparent, biconvex structure of the EYE, enclosed in a capsule and situated behind the IRIS and in front of the vitreous humor (VITREOUS BODY). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the CILIARY BODY is crucial for OCULAR ACCOMMODATION.ElastinUp-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Muscles: Contractile tissue that produces movement in animals.Sertoli Cells: Supporting cells projecting inward from the basement membrane of SEMINIFEROUS TUBULES. They surround and nourish the developing male germ cells and secrete ANDROGEN-BINDING PROTEIN and hormones such as ANTI-MULLERIAN HORMONE. The tight junctions of Sertoli cells with the SPERMATOGONIA and SPERMATOCYTES provide a BLOOD-TESTIS BARRIER.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Matrix Metalloproteinase 20: A secreted matrix metalloproteinase that is the predominant proteolytic activity in the enamel matrix. The enzyme has a high specificity for dental enamel matrix protein AMELOGENIN.Tendons: Fibrous bands or cords of CONNECTIVE TISSUE at the ends of SKELETAL MUSCLE FIBERS that serve to attach the MUSCLES to bones and other structures.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Tissue Scaffolds: Cell growth support structures composed of BIOCOMPATIBLE MATERIALS. They are specially designed solid support matrices for cell attachment in TISSUE ENGINEERING and GUIDED TISSUE REGENERATION uses.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Lanthanum: Lanthanum. The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Fluorescent Antibody Technique, Indirect: A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Cell Shape: The quality of surface form or outline of CELLS.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Seminiferous Epithelium: The epithelium lining the seminiferous tubules composed of primary male germ cells (SPERMATOGONIA) and supporting SERTOLI CELLS. As SPERMATOGENESIS proceeds, the developing germ cells migrate toward the lumen. The adluminal compartment, the inner two thirds of the tubules, contains SPERMATOCYTES and the more advanced germ cells.Blood-Brain Barrier: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Cell Adhesion Molecules, Neuronal: Surface ligands that mediate cell-to-cell adhesion and function in the assembly and interconnection of the vertebrate nervous system. These molecules promote cell adhesion via a homophilic mechanism. These are not to be confused with NEURAL CELL ADHESION MOLECULES, now known to be expressed in a variety of tissues and cell types in addition to nervous tissue.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Dental Enamel Proteins: The proteins that are part of the dental enamel matrix.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Endodeoxyribonucleases: A group of enzymes catalyzing the endonucleolytic cleavage of DNA. They include members of EC 3.1.21.-, EC 3.1.22.-, EC 3.1.23.- (DNA RESTRICTION ENZYMES), EC 3.1.24.- (DNA RESTRICTION ENZYMES), and EC 3.1.25.-.