One of the primary tissue shaping mechanisms that is utilized during development is tissue elongation, which is essential to the formation of the elongated head-to-tail body axis and to the development of many internal organs. In epithelial sheets, cellular processes that drive local changes in cell-cell adhesion can be harnessed by developmental programs to effect macroscopic changes in tissue architecture such as elongation; one example is the systematic remodeling of the germ-band epithelium in drosophila. The prevailing model is that a system of planar polarity of junction-associated proteins drives the necessary symmetry-breaking of junction remodeling; specifically, it has been proposed that line tension generated by actomyosin contraction drives the shrinking and loss of cell-cell interfaces with specific spatial orientation. To develop a more detailed biomechanical characterization of this process, we are measuring the dynamics of junction contraction and growth with quantitative imaging and analytical methods; based on our preliminary results, we hypothesize that junctions remodel not through tension contraction, but through `sliding' type displacement. Since cell topologies and protein dynamics are rapidly changing during tissue elongation, we are developing novel computational approaches to permit the analysis of remodeling behaviors from the level of junction vertices to cells and whole tissue. These should be analytic tools of broad interest to the scientific community. The approaches used in these studies will draw on advanced imaging, computational and biophysical techniques that are just beginning to be applied in Drosophila. The funding of this project will be the first major grant for the newly established lab, and will represent an important step towards the founding of independent research programs.
One of the basic tissue shaping mechanisms that is utilized during embryonic development is tissue elongation, which is essential to the shaping of an elongated body axis, as well as the development of many internal organs, such as the palate and cochlea. It is thought that local failures of the systematic interaction of cells with their neighbors can drive large-scale failures in tissue shaping, which can lead to developmental defects. We seek to identify the local biomechanical mechanisms that direct and regulate successful tissue elongation.
| Vanderleest, Timothy E; Smits, Celia M; Xie, Yi et al. (2018) Vertex sliding drives intercalation by radial coupling of adhesion and actomyosin networks during Drosophila germband extension. Elife 7: |
| Jewett, Cayla E; Vanderleest, Timothy E; Miao, Hui et al. (2017) Planar polarized Rab35 functions as an oscillatory ratchet during cell intercalation in the Drosophila epithelium. Nat Commun 8:476 |
