Contributed talk

Origin of Asymmetry in Tip Cell Mitosis

Christopher Revell, Holly Lovegrove, Shane Herbert, Katie Bentley

Early angiogenesis occurs by chain migration with trailing stalk cells led by active tip cells [Gerhardt et al. (2003)]. Tip cells were long thought to not divide [Gerhardt et al. (2003)]. This has recently been observed not to be the case, but during mitosis, tip cells do not round up, and instead maintain their pre-mitotic shape. This asymmetry in division is hypothesised to facilitate maintenance of tip cell phenotype in only one daughter cell [Costa et al. (2016)], but the mechanisms by which the asymmetry arises have not been elucidated. In this ongoing work, we perform a theoretical and computational investigation of mitotic tip cell shape. Since mitotic rounding is driven by an increase in cell cortical tension [Fischer-Friedrich et al (2014)] and breakdown of focal adhesions, we focus on the cell boundary and utilise the immersed boundary framework [Rejniak (2007)] with variation in local cortical tension. We consider the effect of a short window of global CyclinB1-Cdk1 activity [Santos et al. (2012); Gavet and Pines (2010)] and subsequent production of downstream cortical tension effectors. By modelling the impact of cell shape on the local diffusive flux of tension effectors from the cytoplasm into the cell cortex preceding division, we demonstrate a potential mechanism by which the pre-mitotic morphology of tip cells can affect the local variation of cortical tension, and thus determine mitotic rounding.