The vertebrate tailbud is a dynamic growth zone that gives rise to the trunk and tail. During body elongation, motile tailbud cells undergo an order to disorder transition via EMT as they become mesodermal progenitors and sort into the left and right paraxial mesoderm. Combining quantitative in vivo cell tracking with modeling of cell migration in a tailbud-like geometry, the research group identified anisotropic left-right fluxes after EMT as cells sort into the paraxial mesoderm. At any single timepoint, cell flux is typically asymmetric. This pattern represents intermittent collective cell migration within the disordered mesodermal progenitor domain. The increased disorder in cell motion after EMT frequently switches the direction of the anisotropic cell flows which ensures bilateral symmetry of the spinal column. A two-pronged approach is used to understand the mechanism of symmetric body elongation. The first approach is to identify downstream effectors of the Fgf, Wnt and Bmp signaling pathways that work in conjunction with Cadherin 2 to govern the order to disorder transition in cell motion. Second, the research group examines the general roles of cell adhesion, cytoskeletal contractility and cell polarity in tailbud cell motion. The group will use in silico and in vivo analysis to define the cross- scale mechanism by which noisy genetic and biophysical interactions between cells, acting at different time-scales, produce episodic bilaterally asymmetric collective cell migration at the scale of a few cells that is integrated over time to symmetrically disperse thousands of cells into the paraxial mesoderm.
This project seeks to understand the genetic control of the biomechanics of early spinal column development. The research utilizes quantitative live imaging and in silico modeling to elucidate the mechanisms governing the cell migration and cell sorting that ensure symmetric elongation of the developing spinal column.
