The Digital Fish project: Deciphering the design principles of tissue size, shape, and pattern through microscopy, modeling, and experiments

Sean Megason
Department of Systems Biology
Harvard University


We wish to understand how DNA can program cells to make elaborate tissues in a precise and reproducible way despite inherent physical limits in the underlying computation and communication needed to coordinate across these vast scales. Organismal form is indeed encoded in DNA but not as a “blue print” as often described. Rather form takes shape during development as computations guided by DNA interact with physical processes replete with feedback at all levels. We study this question in the context of the developing zebrafish embryo due to its suitability for timelapse microscopy, genetics, and embryological manipulations. In addition to observational and experimental approaches, which are the mainstay of biology, we are also taking a “constructivist” approach in which we try to recreate developmental processes in mathematical/computational models. Our ultimate muse is the Digital Fish, a computational model that would explain how the genome turns a fertilized egg into an embryo.