Epithelial-mesenchymal interactions and lung branching morphogenesis. Role of polyamines and transforming growth factor ß1

Abstract

Lung branching morphogenesis is a result of epithelial-mesenchymal interactions, which are in turn dependent on extracellular matrix composition and cytokine regulation. Polyamines have recently been demonstrated as able to modify chick embryo skin differentiation. In this work we have examined the effects of putrescine and spermidine during chick embryo lung morphogenesis in organotypic cultures by morphological, histochemical and biochemical examination. To verify the role of polyamines, we used specific inhibitors, such as bis-cyclohexylammonium sulphate and alfa-difluoromethylornithine, and transforming growth factor ß 1 , an ornithine decarboxylase and polyamine stimulator. Our data show that lung morphogenesis is significantly altered following the induced mesenchymal glycosaminoglycan changes. The increase of mesenchymal glycosaminoglycans is correlated with a stimulation of lung development in the presence of polyamines, and with its inhibition when transforming growth factor ß 1 is added to the culture medium. The morphometric data show a uniform 151 increase of both the mesenchyme and epithelial branching with spermidine and putrescine stimulus, whereas the mesenchymal substance alone is significantly increased in apical-median lung sections with transforming growth factor ß 1 and transforming growth factor ß 1 + spermidine lung cultures. Transforming growth factor ß 1 and transforming growth factor ß 1 + spermidine confirm the blocking of epithelial branching formations and fibroblast activation, and show that polyamines are unable to prevent the blocking of epithelial cells due to the inhibitory effect of transforming growth factor ß 1 .

Inhibitory morphogens and monopodial branching of the embryonic chicken lung

“…TGFβ signaling inhibits branching of both mouse and chicken airways (Serra et al, 1994; Serra and Moses, 1995; Zhao et al, 1996; Zhao et al, 1998; Zhao et al, 2000; Stabellini et al, 2001), but disrupting signaling through the receptor only appears to block growth of the airways in explant cultures of the chicken lung. In contrast, blocking TGFβ receptor signaling in culture or in vivo enhances branching of the mouse lung without reportedly affecting growth of the airways (Zhao et al, 1996; Zhao et al, 1998).…”

The design of the avian respiratory system: development, morphology and function

“…Asterisks lungs, Tr trachea, a cervical air sac, b interclavicular air sac, c cranial thoracic air sac, d caudal thoracic air sac, e abdominal air sac, arrows costal sulci, circles ostia et al 2010). Some of the notable studies are on the following: the stimulation of DNA synthesis in the embryonic chick lung and trachea by the epidermal growth factor (EGF) (Goldin and Opperman 1980;Hacohen et al 1998); the expression and distribution of cell-to-cell adhesion molecules (fibronectin and laminin) on the embryonic chick lung cells (Chen et al 1986); the expression of the nuclear factor-kappa-b on epithelial growth and branching of the embryonic chick lung (Muraoka et al 2000); the roles of polyamines and transforming growth factor beta-1 (TGF-b1) on the branching morphogenesis during the development of the embryonic chick lung (Stabellini et al 2001); the effect of the Tbx-4-Fgf-10 system on the separation of the lung bud from the oesophagus in the chicken embryo (Sakiyama et al 2003); the expression of the basic fibroblast growth factor-2 (bFGF-2) in the epithelial and mesenchymal cells of the developing avian lung (Maina et al 2003) (Fig. 26); the role of Wnt-5a signaling molecule in controlling the bronchial and the vascular developments (Loscertales et al 2008); the effect of the diffusion gradient of FGF-10 on the differentiation of the mesenchymal cells and the development of the air sacs (Miura et al 2009); the impairment of the expression of FGF-10, FGFR, and SPRY-2 and the inhibition of FGFR on the branching of the airways and reduction of mesenchymal tissue space (Moura et al 2011) and; the delineation of changes in the expression of FGF-10 and Figs.…”

Evolution of Air Breathing: Oxygen Homeostasis and the Transitions from Water to Land and Sky

“…Embryonic expression of the transcription factor nuclear factor-kappa-β limits growth and branching of the epithelium and mediates mesenchymal-epithelial interactions of multiple genes involved in proliferation and branching, including FGF-10, bone morphogenic protein-4, and transforming growth factor-β1 (560). Other growth factors include basic FGF-2, which is continuously upregulated in epithelial and mesenchymal cells throughout lung development (494), and polyamines (spermidine and putrescine), which uniformly enhance mesenchyme and epithelial branching (728). Miura et al (548) suggested that regional difference between air sac and branched airway development in embryonic chick lung results from differential ventro-dorsal regional diffusion of morphogens.…”