Self-organized fingering instabilities drive the emergence of tissue morphogenesis in digit organoids.
Tsutsumi, R.; Diez, A. N.; Plunder, S.; Kimura, R.; Oki, S.; Takizawa, K.; Akiyama, H.; Mii, Y.; Takada, R.; Takada, S.; Eiraku, M.
Show abstract
Tissue morphogenesis is an emergent phenomenon: macroscopic structures cannot be predicted from a parts list of genes and cells. We examined how digits arise from a spherical limb bud and present a framework linking microscopic behaviors to morphogenesis. To extract digit morphogenesis in vitro, we created a limb-mesenchyme organoid that breaks symmetry and forms digit-like cartilage. Analyzing cell behaviors and iterating with cellular-based models identified sufficient microscopic mechanisms: differential adhesion between Distal and Proximal cells, chemotaxis toward Fgf8b and Wnt3a, and biased traction driving convergent extension. Taking the continuum limit of these behaviors yielded a modified Cahn-Hilliard equation that can describe fingering instability, recapitulating organoid morphogenesis. Taken together, this work suggests that the emergence of "fingers" can be explained as fingering instability.
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