Rules underlying organismal development and coordination of cellular actions

Establish mechanistic rules that explain how local single-cell actions—division, excretion, consumption, and reorganization—coordinate across large multicellular populations to produce complex, functional structures during organismal development.

Background

The paper introduces a differentiable programming framework to learn local, biologically interpretable gene regulatory networks that drive multicellular morphogenesis through chemical signaling, adhesion, and mechanics. Despite extensive empirical knowledge of cell behaviors, a unifying, predictive set of rules linking local cellular decisions to organism-scale form and function has remained elusive.

By differentiating through simulations of a physical model of cell interactions and optimizing gene network parameters, the authors demonstrate learned mechanisms for symmetry breaking, emergent gradients, homogenized growth via mechanical feedback, programmed shape formation, and damage repair. The stated open problem frames the broader motivation for this approach: to uncover general principles governing how microscopic cellular actions coordinate to yield macroscopic developmental architecture.