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Fgf Signaling And Early Lung Development

1744 words - 7 pages

Epithelial-mesenchymal interactions mediate organogenesis, which results from the activation of complex gene networks. Early respiratory development arises from the foregut endoderm and gives rise to tracheal and lung progenitor cells. Recent studies have linked fibroblast growth factor, Wnt, and other signaling pathways to the initial stages of lung development. Cells respond to signaling proteins mainly though transcription factors that ultimately determine cell fate and pattern formation. Gain and loss-of-function studies have facilitated the identification and functionality of molecular components as part of development. Fibroblast growth factor (FGF) signaling plays an important role in the regulatory network present in embryonic pulmonary development. FGF controls cell proliferation, differentiation and pattern formation; however, the interaction of FGF with other signaling pathways is still questioned by researchers. FGF-7 and FGF-10 are important for patterning and growth of the lung bud and are differentially regulated by FGF-1 and FGF-2. Research has shown FGF is an important factor in respiratory development as it regulates the expression of other signaling pathways. Said molecular events involving FGF signaling drive key phases of pulmonary development and thus the understanding of these key segmental mechanisms gives way to new knowledge of pathogenesis involving congenital anomalies, helping to develop innovative therapies to treat disease. Unless specifically mentioned, anything regarding expression patterns and developmental effects of morphogens, transcription and growth factors, or any other developmental factors effecting lung development are referenced from the murine lung. Accordingly, functional relevance of these factors are theorized to exist in the human lung as well.
Classical and recent studies show that pulmonary branching morphogenesis and differentiation result from interactions between epithelial and mesenchymal cells. Complex feedback signaling regulates the patterning and specification of phenotypes. Regulatory signaling controls cell proliferation, differentiation, migration and cell death. Fibroblast grow factors (FGF) are essential components of the gene network that controls pulmonary development(Kimura and Deutsch, 2007). Namely, FGF-10 and FGF-7 play critical roles in branching morphogenesis. FGF-10 is highly concentrated in the distal lung mesenchyme in a pattern that appears to link with other sites initiating bud formation(Cardoso and Lü, 2006).
The development of the lung is highly contested, as the control of growth is not fully understood. It is increasingly clear that in utero conditions during development greatly influence pulmonary organogenesis and any abnormality will be carried through adulthood. At four weeks of gestation the lung appears as a diverticulum and by the sixteenth week of gestation all pre-acinar airways, arteries, and veins have formed(Maeda et al., 2007). Pulmonary...

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