第1288回生物科学セミナー

Mechanical forces influence three-dimensional cell behaviours in the mouse embryo

田尾 嘉誉 博士(The Hospital for Sick Children, Toronto, Canada)

2019年05月31日(金)    16:00-17:30  理学部2号館 講堂   

A fundamental question in developmental biology is the how organs are shaped. Morphogenesis
has long been recognised as an inherently physical process. In recent years, we have been
combining data from live light sheet imaging, a vinculin tension sensor knock-in as a proxy for
cortical tension, and magnetic tweezers to measure tissue-scale elasticity and viscosity within
solid organ primordia such as the limb buds and branchial arches in the mouse embryo. We
showed how physical tissue stress is regulated by developmental pathways to orient cell
rearrangements that remodel ectoderm with new biophysical approaches and genetic tools1,2). We
now tackle the challenge of 3D mesenchymal morphogenesis by using novel biophysical tools we
generated, including a magnetic tweezer system to map tissue stiffness3) and a genetically
encoded FRET-based force sensor to measure cortical forces of individual cells in vivo4). The
emerging data suggest that two modes of cell movement, rearrangements and crawling, both
contribute to collective mesenchymal cell movements that shape organ primordia. Cell
rearrangements can be considered to result from liquid-like rigidity phase properties that are
determined by cellular topologies and oscillations. There is correlative evidence that cell crawling
is oriented by durotaxis, or the movement of cells up a stiffness gradient. In this seminar, I show
our currently research and discuss mechanisms bridging from cooperative multicellular behavior to
shaping organ with a finite element model of morphogenesis.
1) Lau, K., Tao, H., et al., Nat Cell Biol. 17(5):569-579, 2015
2) Wen, J., Tao, H. et al., Biophys J. 112(10):2209-2218, 2017
3) Zhu, M., Tao, H. et al., bioRxiv 412072, 2018
4) Tao, H. et al., Nat Commum. 10(1):1703, 2019