Diverse Roles of Eph/ephrin Signaling in the Mouse Lens

Recent genetic studies show that the Eph/ephrin bidirectional signaling pathway is associated with both congenital and age-related cataracts in mice and humans. We have investigated the molecular mechanisms of cataractogenesis and the roles of ephrin-A5 and EphA2 in the lens. Ephrin-A5 knockout (-/-) mice often display anterior polar cataracts while EphA2(-/-) lenses show very mild cortical or nuclear cataracts at weaning age. The anterior polar cataract of ephrin-A5(-/-) lenses is correlated with multilayers of aberrant cells that express alpha smooth muscle actin, a marker for mesenchymal cells. Only select fiber cells are altered in ephrin-A5(-/-) lenses. Moreover, the disruption of membrane-associated β-catenin and E-cadherin junctions is observed in ephrin-A5(-/-) lens central epithelial cells. In contrast, EphA2(-/-) lenses display normal monolayer epithelium while disorganization is apparent in all lens fiber cells. Immunostaining of ephrin-A5 proteins, highly expressed in lens epithelial cells, were not colocalized with EphA2 proteins, mainly expressed in lens fiber cells. Besides the previously reported function of ephrin-A5 in lens fiber cells, this work suggests that ephrin-A5 regulates β-catenin signaling and E-cadherin to prevent lens anterior epithelial cells from undergoing the epithelial-to-mesenchymal transition while EphA2 is essential for controlling the organization of lens fiber cells through an unknown mechanism. Ephrin-A5 and EphA2 likely interacting with other members of Eph/ephrin family to play diverse functions in lens epithelial cells and/or fiber cells

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Available from STL, Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Взаємозв’язки тривожності та задоволеності життям у осіб з різним рівнем тривоги

Креслова О.В.Взаємозв’язки тривожності та задоволеності життям у осіб з різним рівнем тривоги / О.В. Креслова // Актуальні напрями практичної психології і психотерапії : матеріали VIII Міжнар. наук.- практ. конф. молодих вчених, студентів та аспірантів (м. Харків, 16 груд. 2020 р.). - Харків: ХНУВС, 2020. - С. 96 - 100.В статті розкриваються взаємозв’язки тривожності та задоволеності життям у осіб з різним рівнем тривоги. Висвітлюється поняття тривожності. Тривожність - психічний стан емоційної напруги, настороженості, хвилювання, душевного дискомфорту, підвищеної вразливості при ускладненнях, загостреного почуття провини і недооцінювання себе у ситуаціях очікування, невизначенності або передчуття неясної загрози значущій рівновазі особистості. В статье раскрываются взаимосвязи тревожности и удовлетворенности жизнью у лиц с разным уровнем тревоги. Освещается понятие тревожности. Тревожность – психическое состояние эмоционального напряжения, настороженности, волнения, душевного дискомфорта, повышенной уязвимости при осложнениях, обостренного чувства и недооценивания себя в ситуациях ожидания, неопределенности или предвкушения неясной угрозы значимом равновесии личности. The article reveals the relationship between anxiety and life satisfaction in people with different levels of anxiety. The concept of anxiety is highlighted. Anxiety - a mental state of emotional stress, alertness, anxiety, emotional discomfort, increased vulnerability complications, heightened guilt and self-underestimation situations of expectation, uncertainty or anticipation of a vague threat significant balance of personality

Cloning and developmental expression of amphioxus Dachschund

The nuclear factor dachshund (dac) is a key regulator of eye and leg development in Drosophila.We have cloned a Dachshund homologue from an invertebrate chordate amphioxus (Branchiostoma floridae). Sequence comparison reveals a high degree of similarity of amphioxus Dachshund (AmphiDach) to the known vertebrate and Drosophila dachshund genes. AmphiDach is first expressed in the prospective paraxial mesoderm at the gastrula stage. At the early neurula stage, expression is detected in developing somites and anterior endoderm, but in late neurula transcripts are present exclusively in the most posterior region of the cerebral vesicle and the anterior pharynx endoderm. Then, in larva, AmphiDach is localized in photoreceptive neurons of the frontal eye, infundibular organ, and endostyle as well as in Hesse organs and in nerve cells scattered along the nerve cord. Comparison of Dach expression in amphioxus and vertebrates suggests that such patterns are relatively similar (because they are expressed in somites, photoreceptor cells and CNS), even if expression of AmphiDach in the endostyle has no counterparts in its vertebrate homolog, the thyroid

Abnormal Lens Morphogenesis and Ectopic Lens Formation in the Absence of β-Cateinin Function

β-Catenin plays a key role in cadherin-mediated cell adhesion as well as in canonical Wnt signaling. To study the role of β-catenin during eye development, we used conditional Cre/loxP system in mouse to inactivate β-catenin in developing lens and retina. Inactivation of β-catenin does not suppress lens fate, but instead results in abnormal morphogenesis of the lens. Using BAT-gal reporter mice, we show that β-catenin-mediated Wnt signaling is notably absent from lens and neuroretina throughout eye development. The observed defect is therefore likely due to the cytoskeletal role of β-catenin, and is accompanied by impaired epithelial cell adhesion. In contrast, inactivation of β-catenin in the nasal ectoderm, an area with active Wnt signaling, results in formation of crystallin-positive ectopic lentoid bodies. These data suggest that, outside of the normal lens, β-catenin functions as a coactivator of canonical Wnt signaling to suppress lens fate

Pax-Six-Eya-Dach network during amphioxus development: conservation in vitro but context specificity in vivo

The Drosophila retinal determination gene network occurs in animals generally as a Pax-Six-Eyes absent-Dachshund network (PSEDN). For amphioxus, we describe the complete network of nine PSEDN genes, four of which-AmphiSix1/2, AmphiSix4/5, AmphSix3/6, and AmphiEya-are characterized here for the first time. For amphioxus, in vitro interactions among the genes and proteins of the network resemble those of other animals, except for the absence of Dach-Eya binding. Amphioxus PSEDN genes are expressed in highly stage- and tissue-specific patterns (sometimes conspicuously correlated with the local intensity of cell proliferation) in the gastrular organizer, notochord, somites, anterior central nervous system, peripheral nervous system, pharyngeal endoderm, and the likely homolog of the vertebrate adenohypophysis. In this last tissue, the anterior region expresses all three amphioxus Six genes and is a zone of active cell proliferation, while the posterior region expresses only AmphiPax6 and is non-proliferative. In summary, the topologies of animal PSEDNs, although considerably more variable than originally proposed, are conserved enough to be recognizable among species and among developing tissues; this conservation may reflect indispensable involvement of PSEDNs during the critically important early phases of embryology (e.g. in the control of mitosis, apoptosis, and cell/tissue motility)

Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract

Cell–cell interactions organize lens fiber cells into highly ordered structures to maintain transparency. However, signals regulating such interactions have not been well characterized. We report here that ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell shape and cell–cell interactions. Lens fiber cells in mice lacking ephrin-A5 function appear rounded and irregular in cross-section, in contrast to their normal hexagonal appearance in WT lenses. Cataracts eventually develop in 87% of ephrin-A5 KO mice. We further demonstrate that ephrin-A5 interacts with the EphA2 receptor to regulate the adherens junction complex by enhancing recruitment of β-catenin to N-cadherin. These results indicate that the Eph receptors and their ligands are critical regulators of lens development and maintenance