Multicampus Research Programs and Initiatives (MRPI); a funding opportunity through UC Research Initiatives (UCRI)UC Office of the President
Characterizing the cellular architecture of dynamically remodeling vascular tissue using 3-D image analysis and virtual reconstruction
Epithelial tubules form critical structures in lung, kidney and vascular tissues. However, the processes that control their morphogenesis and physiological expansion and contraction are not well understood. Here we examine the dynamic remodeling of epithelial tubes in vivo using a novel model system: the extracorporeal vasculature of Botryllus schlosseri, in which the disruption of the basement membrane triggers rapid, massive vascular retraction without loss of barrier function. We developed and implemented 3-D image analysis and virtual reconstruction tools to characterize the cellular morphology of the vascular wall in unmanipulated vessels and during retraction. In both control and regressed conditions, cells within the vascular wall were planar polarized, with an integrin- and curvature-dependent axial elongation of cells and a robust circumferential alignment of actin bundles. Surprisingly, we found no measurable differences in morphology between normal and retracting vessels under ECM disruption. However, inhibition of integrin signaling through FAK inhibition caused disruption of cellular actin organization. Our results demonstrate that epithelial tubes can maintain tissue organization even during extreme remodeling events, but that the robust response to mechanical signals – such as the response to loss of vascular tension after ECM disruption - requires functional force sensing machinery via integrin signaling.