“Endodermal Wnt signaling is required for tracheal cartilage formation”

AbstractTracheobronchomalacia is a common congenital defect in which the walls of the trachea and bronchi lack of adequate cartilage required for support of the airways. Deletion of Wls, a cargo receptor mediating Wnt ligand secretion, in the embryonic endoderm using ShhCre mice inhibited formation of tracheal–bronchial cartilaginous rings. The normal dorsal–ventral patterning of tracheal mesenchyme was lost. Smooth muscle cells, identified by Acta2 staining, were aberrantly located in ventral mesenchyme of the trachea, normally the region of Sox9 expression in cartilage progenitors. Wnt/β-catenin activity, indicated by Axin2 LacZ reporter, was decreased in tracheal mesenchyme of Wlsf/f;ShhCre/+ embryos. Proliferation of chondroblasts was decreased and reciprocally, proliferation of smooth muscle cells was increased in Wlsf/f;ShhCre/+ tracheal tissue. Expression of Tbx4, Tbx5, Msx1 and Msx2, known to mediate cartilage and muscle patterning, were decreased in tracheal mesenchyme of Wlsf/f;ShhCre/+ embryos. Ex vivo studies demonstrated that Wnt7b and Wnt5a, expressed by the epithelium of developing trachea, and active Wnt/β-catenin signaling are required for tracheal chondrogenesis before formation of mesenchymal condensations. In conclusion, Wnt ligands produced by the tracheal epithelium pattern the tracheal mesenchyme via modulation of gene expression and cell proliferation required for proper tracheal cartilage and smooth muscle differentiation

Mus musculus: Biomodelo de expressão de Deiodinase (DIO3) e Transtiretina (TTR) no desenvolvimento da placenta

Introduction: Correct functioning of hypothalamic-pituitary-thyroid axis is essential for embryonic-fetal growth and development, as it is involved in tissue differentiation, brain and somatic development, bone maturation and metabolic regulation. Maternal thyroid hormones passage to the fetus through the placenta depends on transmembrane transporters, deiodinase enzymes (DIO2 and DIO3) and carrier proteins (TTR). Objective: Identify DIO3 and TTR expression within placental layers of Mus musculus E10.5, E12.5 and E14.5. Methods: Placental structure, DIO3 and TTR expression were evaluated using histochemistry and immunofluorescence techniques. Results: We found that the three placental layers, labyrinth zone, junctional zone, and decidua were present since E10.5. At E12.5 placental final conformation was observed. DIO3 and TTR were detected in the three stages with a predominance in the labyrinth. Conclusion: DIO3 and TTR are expressed throughout the establishment and maturation of mouse placenta. Mice are a useful tool for studying how thyroid hormones are transported from maternal to fetal circulation at the placenta.Introducción: El correcto funcionamiento del eje hipotálamo-hipófisis-tiroides es indispensable para el crecimiento y desarrollo embrionario-fetal, al intervenir en la diferenciación de los tejidos, el desarrollo cerebral y somático, la maduración ósea y la regulación del metabolismo. El paso de las hormonas tiroideas maternas al feto a través de la placenta depende de transportadores transmembrana, enzimas desyodinasas (DIO2 y DIO3) y proteínas transportadoras (TTR). Objetivo: Identificar las zonas de expresión de DIO3 y TTR en la placenta de ratón Mus musculus E10.5, E12.5, E14.5.  Métodos: La estructura placentaria y expresión de DIO3 y TTR fueron evaluadas con técnicas histoquímicas e inmunofluorescencia. Resultados: Desde E10.5 se encontraron las tres zonas placentarias, laberinto, zona de unión y decidua. En E12.5 se observó la conformación placentaria definitiva. DIO3 y TTR fueron detectadas en los tres estadios, con predominio en la zona del laberinto. Conclusión: DIO3 y TTR se expresan a lo largo del establecimiento y maduración de la placenta de ratón. El biomodelo murino es una herramienta útil para el estudio del transporte placentario de hormonas tiroideas desde la circulación materna a la fetal.Introdução: O correto funcionamento do eixo hipotálamo-hipófise-tireoide é essencial para o crescimento e desenvolvimento embrionário-fetal, pois intervém na diferenciação dos tecidos, desenvolvimento cerebral e somático, maturação óssea e regulação do metabolismo. A passagem dos hormônios tireoidianos maternos para o feto através da placenta depende de transportadores transmembranas, enzimas deiodinase (DIO2 e DIO3) e proteínas transportadoras (TTR). Objetivo: Identificar as zonas de expressão de DIO3 e TTR na placenta de rato Mus musculus E10.5, E12.5, E14.5. Métodos: A estrutura placentária e a expressão de DIO3 e TTR foram avaliadas com técnicas histoquímicas e imunofluorescência. Resultados: De E10.5 as três zonas placentárias, labirinto, zona de união e decídua foram encontradas. Em E12.5 a conformação definitiva da placenta foi observada. O DIO3 e o TTR foram detectados nas três fases, com predomínio na área do labirinto. Conclusão: DIO3 e TTR são expressos ao longo do estabelecimento e maturação da placenta de rato O biomodelo murino é uma ferramenta útil para o estudo do transporte placentário dos hormônios tireoidianos da circulação materna para a fetal

StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation

Recent studies have demonstrated that human stearoylCoA desaturase-1 (SCD1), a Δ9-desaturase that converts saturated fatty acids (SFA) into monounsaturated fatty acids, controls the rate of lipogenesis, cell proliferation and tumorigenic capacity in cancer cells. However, the biological function of stearoylCoA desaturase-5 (SCD5), a second isoform of human SCD that is highly expressed in brain, as well as its potential role in human disease, remains unknown. In this study we report that the constitutive overexpression of human SCD5 in mouse Neuro2a cells, a widely used cell model of neuronal growth and differentiation, displayed a greater n-7 MUFA-to-SFA ratio in cell lipids compared to empty-vector transfected cells (controls). De novo synthesis of phosphatidylcholine and cholesterolesters was increased whereas phosphatidylethanolamine and triacylglycerol formation was reduced in SCD5-expressing cells with respect to their controls, suggesting a differential use of SCD5 products for lipogenic reactions. We also observed that SCD5 expression markedly accelerated the rate of cell proliferation and suppressed the induction of neurite outgrowth, a typical marker of neuronal differentiation, by retinoic acid indicating that the desaturase plays a key role in the mechanisms of cell division and differentiation. Critical signal transduction pathways that are known to modulate these processes, such epidermal growth factor receptor (EGFR)Akt/ERK and Wnt, were affected by SCD5 expression. Epidermal growth factor-induced phosphorylation of EGFR, Akt and ERK was markedly blunted in SCD5-expressing cells. Furthermore, the activity of canonical Wnt was reduced whereas the non-canonical Wnt was increased by the presence of SCD5 activity. Finally, SCD5 expression increased the secretion of recombinant Wnt5a, a non-canonical Wnt, whereas it reduced the cellular and secreted levels of canonical Wnt7b. Our data suggest that, by a coordinated modulation of key lipogenic pathways and transduction signaling cascades, SCD5 participates in the regulation of neuronal cell growth and differentiation