Harnessing mechanics: Apoptosis and its mechanical role in cell fate determination

 

Yusuke TOYAMA (遠山 祐典)

Mechanobiology Institute, National University of Singapore

Department of Biological Sciences, National University of Singapore

 

Apoptosis, also known as programmed cell death, is a crucial mechanism that ensures the removal of unnecessary or damaged cells during embryonic development, tissue homeostasis, and certain pathological conditions. When a cell undergoes apoptosis within a tissue, it is extruded from its neighboring non-dying cells. Numerous laboratories, including our own, have demonstrated that cell extrusion is facilitated by the formation and contraction of actomyosin cables in the dying and neighboring cells [1-5]. This process leads to changes in mechanical tension in the neighboring cells. However, the way this modulation of tissue tension in the non-dying neighboring cells influences their own cellular function and cell fate remains largely unknown.

In this talk, I will present our latest findings regarding how mechanical tension in the surrounding tissue is altered in a wavelike manner as a result of apoptosis, as well as how this propagation of forces triggers cell cycle progression and proliferation in the neighboring cells [6]. If time permits, I will also share our unpublished results, which shed light on the involvement of immune cells in the process of apoptotic cell extrusion.

 

[1] Thomas M, Ladoux B, Toyama Y*. “Desmosomal junctions govern tissue integrity and actomyosin contractility in apoptotic cell extrusion” Current Biology 26, 2942-50 (2020)

[2] Saw TB, Doostmohammadi A, Nier V, Kocgozlu L, Thampi S, Toyama Y, Marcq P, Lim CT, Yeomans JM, Ladoux B. “Topological defects in epithelia govern cell death and extrusion” Nature, 544, 212–216 (2017)

[3] Teng X, Qin L, Le Borgne R, Toyama Y*. “Remodeling of adhesion and modulation of mechanical tensile forces during apoptosis in Drosophila epithelium.” Development 144, 95-105 (2017)

[4] Kocgozlu L, Saw TB, Le AP, Yow I, Shagirov M, Wong E, Mège RM, Lim CT, Toyama Y*, Ladoux B*. “Epithelial cell packing induces distinct modes of cell extrusions” Current Biology 26, 2942-50 (2016)

[5] Toyama, Y, Peralta, XG, Wells, AR, Kiehart, DP, Edwards, GS. “Apoptotic force and tissue dynamics during Drosophila embryogenesis” Science 321, 1683-1686 (2008).

[6] Kawaue T, Yow I, Pan Y, Le AP, Lou Y, Loberas M, Shagirov M, Teng X, Prost J, Hiraiwa T, Ladoux B, Toyama Y*. “Inhomogeneous mechanotransduction defines the spatial pattern of apoptosis-induced compensatory proliferation” Developmental Cell, 58, 267–277 (2023)