Claudins: unlocking the code to tight junction function during embryogenesis and in disease.
ABSTRACT Claudins are the structural and molecular building blocks of tight junctions. Individual cells express more than one claudin family member, which suggests that a combinatorial claudin code that imparts flexibility and dynamic regulation of tight junction function could exist. Although we have learned much from manipulating claudin expression and function in cell lines, loss-of-function and gain-of-function experiments in animal model systems are essential for understanding how claudin-based boundaries function in the context of a living embryo and/or tissue. These in vivo manipulations have pointed to roles for claudins in maintaining the epithelial integrity of cell layers, establishing micro-environments and contributing to the overall shape of an embryo or tissue. In addition, loss-of-function mutations in combination with the characterization of mutations in human disease have demonstrated the importance of claudins in regulating paracellular transport of solutes and water during normal physiological states. In this review, we will discuss specific examples of in vivo studies that illustrate the function of claudin family members during development and in disease.
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ABSTRACT: The neural crest (NC) is a remarkable transient structure in the vertebrate embryo that gives rise to a highly versatile population of pluripotent cells that contribute to the formation of multiple tissues and organs throughout the body. In order to achieve their task, NC-derived cells have developed specialized mechanisms to promote (1) their transition from an epithelial to a mesenchymal phenotype, (2) their capacity for extensive migration and cell proliferation, and (3) their ability to produce diverse cell types largely depending on the microenvironment encountered during and after their migratory path. Following embryogenesis, these same features of cellular motility, invasion, and proliferation can become a liability by contributing to tumorigenesis and metastasis. Ample evidence has shown that cancer cells have cleverly co-opted many of the genetic and molecular features used by developing NC cells. This review focuses on tumors that arise from NC-derived tissues and examines mechanistic themes shared during their oncogenic and metastatic development with embryonic NC cell ontogeny. Developmental Dynamics, 2014. © 2014 Wiley Periodicals, Inc.Developmental Dynamics 11/2014; 244(3). DOI:10.1002/dvdy.24226 · 2.67 Impact Factor
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ABSTRACT: Claudins are one of the major groups of transmembrane proteins that play crucial roles in tight junctions. In addition to their function in regulation of paracellular permeability, claudins are also involved in a number of biological processes related to pathogen infection, embryonic development, organ development and hypoxia response. Despite its importance, analyses of claudin genes in channel catfish have not been systematically performed. In this study, a total of 52 claudin genes were identified and characterized in channel catfish. Phylogenetic analyses were conducted to determine their identities and identify a number of lineage-specific claudin gene duplications in channel catfish. Expression profiles of catfish claudin genes in response to enteric septicemia of catfish (ESC) disease and hypoxia stress were determined by analyzing existing RNA-Seq datasets. Claudin genes were significantly down-regulated in the intestine at 3 h post-infection, indicating that pathogens may disrupt the mucosal barrier by suppressing the expression of claudin genes. A total of six claudin genes were significantly regulated in the gill after hypoxia stress. Among them, the expression of cldn-11b and cldn-10d were dramatically altered when comparing hypoxia tolerant fish with intolerant fish, though their specific roles involved in response to hypoxia stress remained unknown.Comparative Biochemistry and Physiology Part D Genomics and Proteomics 01/2015; 13C. DOI:10.1016/j.cbd.2015.01.002 · 2.82 Impact Factor
Article: The Blood-Brain Barrier[Show abstract] [Hide abstract]
ABSTRACT: Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.Cold Spring Harbor perspectives in biology 01/2015; 7(1). DOI:10.1101/cshperspect.a020412 · 8.23 Impact Factor