Self-organization of mitotic waves depends on the spatial geometry of the system

Lendert Gelens
Laboratory of Dynamics in Biological Systems Department of Cellular and Molecular Medicine KU Leuven, Campus Gasthuisberg O&N1 Herestraat 49, room 08.326, B-3000 Leuven Belgium

Whether a cell will grow and divide is a highly regulated decision that is controlled by a large and complex network of genes and proteins. Our understanding of how these network components collectively work together in space and time is still limited. In our lab, we combine theory of nonlinear dynamics and complex systems with biological experiments in order to gain new insights into cell cycle regulation. Here, I will discuss our work on cell division coordination in frog embryos. Upon fertilization, the early Xenopus leavis frog egg quickly divides about ten times to go from a single cell with a diameter of a millimeter to several thousands of cells of somatic cell size (tens of microns). Using frog cell-free extracts, one can reconstitute in vitro the biochemical reactions that regulate these clock-like cell divisions. On the one hand, such extract experiments allow us to identify how the presence of feedback loops in the molecular network ensures robust cell cycle oscillations. On the other hand, we find that cell division is spatially coordinated via biochemical waves, whose properties depend on the dimensions of the spatial environment. By carrying out experiments in Teflon tubes of varying diameter, we show that mitotic waves are driven by an internal pacemaker in thinner tubes, while they are boundary-driven in thicker tubes. We show how changing the spatial geometry of the system effectively tunes the relative strength of two pacemaker regions, thus reversing the direction of propagation of mitotic waves.