Engineering morphogenesis of cell clusters with differentiable programming

Abstract

Understanding the rules underlying organismal development is a major unsolved problem in biology. Each cell in a developing organism responds to signals in its local environment by dividing, excreting, consuming, or reorganizing, yet how these individual actions coordinate over a macroscopic number of cells to grow complex structures with exquisite functionality is unknown. Here we use recent advances in automatic differentiation to discover local interaction rules and genetic networks that yield emergent, systems-level characteristics in a model of development. We consider a growing tissue with cellular interactions are mediated by morphogen diffusion, differential cell adhesion and mechanical stress. Each cell has an internal genetic network that it uses to make decisions based on its local environment. We show that one can simultaneously learn parameters governing the cell interactions and the genetic network for complex developmental scenarios, including the symmetry breaking of an embryo from an initial cell, the creation of emergent chemical gradients,homogenization of growth via mechanical stress, programmed growth into a prespecified shape, and the ability to repair from damage. When combined with recent experimental advances measuring spatio-temporal dynamics and gene expression of cells in a growing tissue, the methodology outlined here offers a promising path to unravelling the cellular basis of development.