Keisuke Ishihara

How do the different body axes emerge from a fertilized egg to make an animal? Organ reconstitution is a powerful approach to study how a group of cells “pattern themselves” (Ishihara et al. 2018). Using stem cells, I grow neural tube organoids and study how the dorsal-ventral body axis is established in the absence external tissues (Meinhardt et al. 2014, Ishihara et al. 2017). By default, these organoids harbor dorsal identity, but treatment with retinoic acid initiates a self-organizing circuit that results in the localized expression of the ventral marker FoxA2. To study the dynamics of this spontaneous symmetry breaking at single cell resolution, I am applying light sheet microscopy on organoids made from FoxA2-Venus cells. In addition, I am investigating the molecular and physical basis of how FoxA2+ cells communicate with each other. (with Elena Gromberg and Teresa Krammer, Elly Tanaka group)

Physical extremes in biology are interesting. The large cytoplasm of frog eggs is organized by radial arrays of microtubules called asters. Asters grow, interact and position themselves to help the frog egg find its division plane. As a graduate student in Tim Mitchison’s group, I asked how microtubule asters grow rapidly to one millimeter in diameter. By reconstituting asters in frog egg extract and imaging their growth, I found that new microtubules are nucleated at positions far from the centrosome (Ishihara et al., 2014). In collaboration with Kirill Korolev, I constructed a theoretical model of aster growth and tested its prediction by experiments (Ishihara et al., 2016). This led us to reconsider the textbook model and propose that large microtubule asters are a meshwork of short, interacting, self-amplifying microtubules.

More recently, two additional projects have come out from my PhD research – one related to the theory of traveling waves (Ishihara et al., 2020 New J. of Phys.) and one report on the spatial regulation of microtubule depolymerization (Ishihara et al., 2021 Mol. Bio. Cell).