Membrane-tethered syntaxin-4 locally abrogates E-cadherin function and activates Smad signals, contributing to asymmetric mammary epithelial morphogenesis.

Spatial and temporal epithelial-mesenchymal transition (EMT) is a critical event for the generation of asymmetric epithelial architectures. We found that only restricted cell populations in the morphogenic mammary epithelia extrude syntaxin-4, a plasmalemmal t-SNARE protein, and that epithelial cell clusters with artificial heterogenic presentation of extracellular syntaxin-4 undergo asymmetric morphogenesis. A previous study revealed that inducible expression of cell surface syntaxin-4 causes EMT-like cell behaviors in the clonal mammary epithelial cells, where laminin-mediated signals were abolished so that cells readily succumb to initiate EMT.

Sulfated glycosaminoglycans and non-classically secreted proteins, basic FGF and epimorphin, coordinately regulate TGF-β-induced cell behaviors of human scar dermal fibroblasts.

Background: Upon skin injuries, dermal fibroblasts actively produce transforming growth factor-β (TGF-β), which leads to the formation of α-smooth muscle actin (αSMA)-positive granulation tissues. The hyperplasia or incomplete regression of these tissues subsequently causes scar formation in the skin, where sulfated glycosaminoglycans (GAGs), side chains of unique proteoglycans, are supposed to play important roles.

Objective: The aim of this study is to clarify the effects of sulfated GAGs on dermal cell behaviors triggered by the TGF-β signaling, along with its possible regulators basic fibroblast growth factor (bFGF) and cell surface epimorphin.

Membrane translocation of t-SNARE protein syntaxin-4 abrogates ground-state pluripotency in mouse embryonic stem cells.

Embryonic stem (ES) and induced pluripotent stem (iPS) cells are attractive tools for regenerative medicine therapies. However, aberrant cell populations that display flattened morphology and lose ground-state pluripotency often appear spontaneously, unless glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK1/2) are inactivated. Here, we show that membrane translocation of the t-SNARE protein syntaxin-4 possibly is involved in this phenomenon.

Extracellularly Extruded Syntaxin-4 Binds to Laminin and Syndecan-1 to Regulate Mammary Epithelial Morphogenesis.

Epithelial morphogenesis in the mammary gland proceeds as a consequence of complex cell behaviors including apoptotic cell death and epithelial-mesenchymal transition (EMT); the extracellular matrix (ECM) protein laminin is crucially involved. Syntaxins mediate intracellular vesicular fusion, yet certain plasmalemmal members have been shown to possess latent extracellular functions. In this study, the extracellular subpopulation of syntaxin-4, extruded in response to the induction of differentiation or apoptosis in mammary epithelial cells, was detected.

A newly established culture method highlights regulatory roles of retinoic acid on morphogenesis and calcification of mammalian limb cartilage.

During mammalian embryogenesis, sclerotome-derived chondrocytes in the limb bud are arranged into a complicated bone shape with specific areas undergoing hypertrophy and calcification, creating a region-specific mineralized pattern in the cartilage. To follow chondrogenesis progression in vitro, we isolated limb cartilage from mice on embryonic day 13 (E13) and cultured it at the air-liquid interface after microsurgical removal of the ectoderm/epidermis. Explants underwent proper morphogenesis, giving rise to complete templates for limb bones in vitro.