Anabaena, a multicellular model for cyanobacterial cell biology and biotechnology

Heterocyst-forming cyanobacteria (order Nostocales) are a monophyletic group of organisms that grow as filaments usually made of dozens to hundreds of cells (termed vegetative cells) that can perform oxygenic photosynthesis. Under combined nitrogen deficiency, some cells in the filament differentiate into N₂-fixing heterocysts, which do not produce oxygen and, indeed, keep a microoxic environment appropriate for the expression and functioning of the N₂-fixing enzyme, nitrogenase. Thus, in the diazotrophic filament, oxygenic photosynthesis and N₂ fixation are segregated into two different cell types, vegetative cells and heterocysts, which require intercellular molecular exchange to feed each other with fixed nitrogen and reduced carbon, respectively. The current understanding of heterocyst biology, including regulation of heterocyst differentiation, which also involves intercellular signaling, is the result of studying mainly a few strains of the genus Anabaena. Here, we review the classical studies that established Anabaena as a model for the Nostocales and clarified the basics of N₂ fixation in these organisms. Then, we show how molecular genetics came into the scene and how it was complemented by genomic analysis. This, together with the introduction of modern cell biology approaches, led to a renewed understanding of cellular differentiation and unraveled a system for intercellular communication that is unique in the biological world. In turn, the new accumulated knowledge on Anabaena physiology and genetics makes these organisms an excellent system for the development of new synthetic biology tools that will be crucial for their use in biotechnology.