Cell, organ, and body shapes vary in the context of natural selection. Identification of the cellular and molecular mechanisms underlying these differences is important for understanding how changes in the shapes of cells affect the emergence of new shapes in organisms and their component parts. Dr. Veeman?s research program defines the cell and molecular behaviors controlling tapering in an organ that is thinner at its end(s) than at its middle, and he has chosen the notochord (a rod shaped axial structure) in Ciona (a sea squirt) as his experimental system. Ciona provides an excellent model for studying these processes, because it has a distinctively tapered shape and consists of only 40 cells that can easily be visualized in their entirety. Ciona notochord tapering involves asymmetric cell division, meaning that cells divide to give daughter cells of unequal size. It is generally thought that positioning of the cell division plane is specified by molecular cues, but the novel idea that is tested here is that a cellular cue (the shape of the mother cell) can also control asymmetric division. The experiments work toward a quantitative understanding of how subtle local changes in distinct cell behaviors can lead to major effects on organ and body shape (and thus to evolvability). In addition to his research, Dr. Veeman is actively involved in training and outreach. He will also engage the public through exhibitions of images from local biologists that inspire scientific storytelling.
The invertebrate chordate Ciona is an emerging model for the systems biology of embryonic morphogenesis and has distinct advantages for understanding how local changes in cell shape and behavior affect the emergence of shape at the level of entire organs and body axes. The Ciona notochord cells form a long tapered rod running the length of the larval tail. Many animal organs, limbs, appendages and body axes are tapered for important biomechanical reasons, but the mechanisms controlling taper are largely unknown. One key element of Ciona notochord taper is the tendency of cells closer to the ends of the notochord to be progressively smaller in volume than cells in the middle. The proposed experiments address the cellular and molecular mechanisms establishing this taper. A central hypothesis is that many of the asymmetric divisions in the notochord may not involve a specific molecular cue displacing the mitotic spindle, but instead may reflect ubiquitous spindle centering mechanisms acting in asymmetrically shaped cells. Wedge-shaped and other asymmetrically shaped cells are common in developing embryos, but the implications of cell shape for spindle positioning and cytokinesis are not currently understood. The research team proposes both descriptive and functional experiments to test this important relationship. Aim 1 tests whether asymmetric cell division is the only mechanism at work in controlling notochord cell volume, or whether lineage-specific changes in volume may also be important. Aim 2 tests potential mechanisms of asymmetric division in the notochord, including the PAR and LGN/NUMA pathways, and also tests a novel hypothesis directly connecting asymmetric division to cell shape. Aim 3 tests whether several pathways involved in notochord morphogenesis have specific roles in the cell behaviors giving rise to taper.
