Claudin‐6: A novel tight junction molecule is developmentally regulated in mouse embryonic epithelium

Abstract

Embryonic stem (ES) cells differentiating into embryoid bodies (EBs) have been shown to mimic events of very early development and have become a convenient system in which to identify and study early epithelial specific genes. We describe here the primary structure of a mouse epithelial-specific tight junction gene and its expression patterns in differentiating ES cell-derived EBs in vitro. Sequencing The results indicate that Claudin-6 is one of the earliest molecules to be expressed in ES cells committed to the epithelial fate, and the onset of its expression coincides with the expression of the early epithelial marker, keratin 8 (K8). The initiation of expression of Claudin-6 in vitro is dependent upon plating density as well as serum components. In addition, it was found that Claudin-6 expression is inhibited by Noggin, the Bone Morphogenic Protein (BMP)-signalling pathway inhibitor, suggesting that BMPs may be involved in Claudin-6 expression and epithelialization. These studies establish Claudin-6 as a very early marker of epithelialization and provide evidence that the BMP signalling pathway may be one of the ways that its expression is regulated. These studies also support the power of in vitro ES cell technology to identify and screen novel molecules involved in the early epithelialization of the mouse embryo.

Claudin-6, -10d, and -10e contribute to seawater acclimation in the euryhaline puffer fishTetraodon nigroviridis

“…This would indicate that cldn-6 may play a role in the physiology of the blood-brain barrier in fishes or other processes in the nervous tissue. In contrast, cldn-6 is absent from most adult mammalian tissues (including the brain) and its expression has been associated with prenatal developmental stages (Abuazza et al, 2006;Fujita et al, 2006;Morita et al, 1999;Morita et al, 2002;Reyes et al, 2002;Turksen and Troy, 2001;Turksen and Troy, 2002). Nevertheless, in adult mammalian tissues, Cldn-6 has been reported in the kidney (Morita et al, 1999;Zhao et al, 2008), taste buds (Michlig et al, 2007) and mammary gland (Quan and Lu, 2003), and in embryos and neonates, cldn-6 has been found in a variety of tissues that include the kidney (Zhao et al, 2008), the periderm of -ATPase (NKA; green) and (B) Cldn-6 (red) immunoreactivity show (C) colocalization of these proteins in ionocytes (arrowheads) with some peripheral punctate Cldn-6 staining around ionocytes (arrows).…”

Claudin 6: a novel surface marker for characterizing mouse pluripotent stem cells

“…We identified one particularly interesting molecule, Claudin 6 (Cldn6), which was consistently expressed at elevated levels in stem cells relative to non-stem cells (Supplementary information, Table S3). Cldn6, a member of the tight junction family, has been reported to play an important role during mouse embryonic epithelium formation [4] and the development of endodermal tissues [5]. The level of Cldn6 expression is correlated with dedifferentiation and malignant proliferation of epithelial cells [6,7].…”

Up-Regulation of the Claudin-6 Gene in Adipogenesis

“…Using an mRNA differential display method, we found that claudin-6, a member of the claudin multigene family (about 23 kDa) of tight junction (TJ) molecules, is differentially expressed in subcutaneous and visceral adipose tissues of mice. Claudin-6 is known to be present in embryonic epithelia, 4,5) and overexpression of claudin-6 in transgenic mice generates a defective epidermal permeability barrier. 6) Epithelial TJ constitutes a barrier both to the passage of ions and molecules through the paracellular pathway and to the movement of proteins and lipids between the apical and the basolateral domains of the plasma membrane.…”