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  • Immuno-localization of CD44 and osteopontin in developing human kidney. 18787423

    CD44 is observed in ureteric bud structures and is implicated in branching morphogenesis during early mouse renal development. Healthy adult kidney demonstrates minimal CD44, but CD44 is up-regulated in renal diseases. CD44 may mediate binding of calcium oxalate crystals to tubular epithelia via the ligands osteopontin (OPN) and hyaluronan. Because 15% of premature infants develop nephrocalcinosis, developmental tubular CD44 expression might promote nephrocalcinosis. We studied CD44 and OPN immuno-localization in developing human kidney by immunohistochemical analysis. Human renal tissue between 18 and 40 wk of gestation showed CD44 immuno-localization in ureteric buds, with staining decreasing with increasing gestational age; CD44 was rarely observed in developing renal tubules. OPN was diffusely observed in proximal tubules, rarely observed in distal tubules, ureteric buds or metanephric structures. These data support the role of CD44 in early human nephron formation and branching morphogenesis. Rare CD44 staining in developing tubular epithelium suggests no role for CD44 in promoting calcium oxalate adherence to tubular epithelia in premature infants. Immuno-localization of OPN in tubules supports its role in tubular differentiation, but OPN does not seem to be necessary during early nephron formation.
    Document Type:
    Reference
    Product Catalog Number:
    07-068
  • Epicardial calcineurin-NFAT signals through Smad2 to direct coronary smooth muscle cell and arterial wall development. 23946498

    Congenital coronary artery anomalies produce serious events that include syncope, arrhythmias, myocardial infarction, or sudden death. Studying the mechanism of coronary development will contribute to the understanding of the disease and help design new diagnostic or therapeutic strategies. Here, we characterized a new calcineurin-NFAT signalling which specifically functions in the epicardium to regulate the development of smooth muscle wall of the coronary arteries.Using tissue-specific gene deletion, we found that calcineurin-NFAT signals in the embryonic epicardium to direct coronary smooth muscle cell development. The smooth muscle wall of coronary arteries fails to mature in mice with epicardial deletion of calcineurin B1 (Cnb1), and accordingly these mutant mice develop cardiac dysfunction with reduced exercise capacity. Inhibition of calcineurin at various developmental windows shows that calcineurin-NFAT signals within a narrow time window at embryonic Day 12.5-13.5 to regulate coronary smooth muscle cell development. Within the epicardium, NFAT transcriptionally activates the expression of Smad2, whose gene product is critical for transducing transforming growth factor β (TGFβ)-Alk5 signalling to control coronary development.Our findings demonstrate new spatiotemporal and molecular actions of calcineurin-NFAT that dictate coronary arterial wall development and a new mechanism by which calcineurin-NFAT integrates with TGFβ signalling during embryonic development.
    Document Type:
    Reference
    Product Catalog Number:
    07-068