The role of mechanical stresses in regulation of FGF10 signaling in embryonic mouse lung development

Stanton, Alice Elizabeth [Browse]
Senior thesis
46 pages


Nelson, Celeste M. [Browse]
Princeton University. Department of Chemical and Biological Engineering [Browse]
Class year
Restrictions note
Walk-in Access. This thesis can only be viewed on computer terminals at the Mudd Manuscript Library.
Summary note
Branching morphogenesis of organs such as the lung, mammary gland, and kidney involves an intricate process [4] that is influenced by a number of different signaling pathways [5] and mechanical stimuli, including pressure, tension, compression, and shear stress [6]. New branch initiation is guided in part by fibroblast growth factor-10 (FGF10) secretion in the mesenchyme, which is regulated by Sprouty2 (Spry2) [2]. However, the relationship between these chemical factors and the mechanical stresses, and their effect on embryonic development of the mouse lung, remain largely enigmatic. When this developmental process does not occur as expected, serious birth defects can result. To gain a better understanding of this complex relationship, I investigated how hydrostatic pressure affects FGF10 signaling and lung development of the early embryo. An ex vivo culture system was created that permits the modulation of hydrostatic pressure and comparison of morphologies. 3D surface models were generated to obtain quantitative information about the morphology. Allometry, the study of how an organism’s size scales with other characteristic variables, was applied to the explants as a method for quantitatively comparing the morphologies [7]. Lung explants were successfully cultured over 72 hours. Hydrostatic pressure was found to alter lung growth, overall tissue architecture, and FGF10 signaling. Increases in hydrostatic pressure decrease the rate of growth, thereby decreasing the branching and growth of the lungs, but not irreversibly. Heightened hydrostatic pressure also decreases FGF10 expression and increases Spry2 expression. Mechanical stresses affect the signaling pathways, branching, and growth essential for embryonic development of the mouse lung. Further characterization of the growth and gene expression of lungs and the role of mechanical stresses will lead to a better understanding of branching morphogenesis.

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