RESEARCH ARTICLE An Integrative Approach for Modeling and Simulation of Heterocyst Pattern Formation in Cyanobacteria Filaments

Heterocyst differentiation in cyanobacteria filaments is one of the simplest examples of cel-lular differentiation and pattern formation in multicellular organisms. Despite of the many ex-perimental studies addressing the evolution and sustainment of heterocyst patterns and the knowledge of the genetic circuit underlying the behavior of single cyanobacterium under ni-trogen deprivation, there is still a theoretical gap connecting these two macroscopic and mi-croscopic processes. As an attempt to shed light on this issue, here we explore heterocyst differentiation under the paradigm of systems biology. This framework allows us to formu-late the essential dynamical ingredients of the genetic circuit of a single cyanobacterium into a set of differential equations describing the time evolution of the concentrations of the relevant molecular products. As a result, we are able to study the behavior of a single cya-nobacterium under different external conditions, emulating nitrogen deprivation, and simu-late the dynamics of cyanobacteria filaments by coupling their respective genetic circuits via molecular diffusion. These two ingredients allow us to understand the principles by which heterocyst patterns can be generated and sustained. In particular, our results point out that