Thank you Mark! Yes, I will probably talk about this story!

This work was a collaboration with Toshihiko Fujimori, Noriyuki Kinoshita, and a former PhD student Thanh Phuong Nguyen, who supported the imaging and laser ablation experiments. And special thanks to Mikio who gave me the freedom to pursue this issue in his lab! (13/n)

Many important questions remain. How do their neighbors recognize junction-deficient cells? How does cell compression lead to apoptosis? What are the physiological functions of this process in vivo? These issues will keep us busy in the future! (12/n)

Together with an accompanying preprint by @levayerr.bsky.social that shows that interfacial tension or growth are sufficient to drive mechanical cell competition, these results establish the importance of interfacial tension in mechanical cell competition. (11/n)
www.biorxiv.org/content/10.1...

Further exploring the underlying molecular mechanisms, we found that mechanosensing in the ‘winner’ cells via the Hippo signaling and an adherens junction component afadin was required to eliminate ZO-1/ZO-2 double KO cells. (10/n)

These results suggested that the ‘loser’ cells are eliminated by mechanical compression. Indeed, when we modified the coculture ratio, we found that ZO-1/ZO-2 double KO cells (magenta) needed to be surrounded by normal cells (green) to be eliminated. (9/n)

ROCK was required to form supracellular actomyosin cables formed in the normal cells at the clone boundary. The actomyosin cables constricted in a purse-string-like manner to eliminate ZO-1/ZO-2 double KO cells. (8/n)

We performed a chemical compound library screening to elucidate the underlying molecular mechanisms and found that ROCK plays a key role in eliminating ZO-1/ZO-2 double KO cells. (7/n)

Importantly, epithelial barrier function measured by transepithelial electric resistance progressively recovered as the elimination proceeded. These results suggested that cell-cell junction-deficient cells are eliminated from epithelia to maintain epithelial barrier homeostasis. (6/n)

Indeed, by carefully observing the time course of the coculture, we found that ZO-1/ZO-2 double KO cells are eliminated by apoptosis when surrounded by normal cells! (5/n)

At first, we thought it was a simple mistake, but finally, we realized that some KO cells remained at the edge of the colonies. This observation reminded us of the cell competition phenomena initially characterized in Drosophila. (4/n)

Having a background in Drosophila genetics, I decided to mix the KO cells with normal cells, akin to the mosaic analysis in flies, and compare the phenotype. However, we repeatedly encountered a problem – a failure to recover ZO-1/ZO-2 double KO cells in the coculture. (3/n)

This project started when I joined Mikio Furuse’s lab in National Institute for Physiological Sciences. ZO-1/ZO-2 double KO cells were just established in the lab then, and I decided to look at their phenotypes. (2/n)

Please add me!