Interaction network among factors involved in heterocyst-patterning in cyanobacteria

The genetically regulated pattern of heterocyst formation in multicellular cyanobacteria represents the simplest model to address how patterns emerge and are established, the signals that control them, and the regulatory pathways that act downstream. Although numerous factors involved in this process have been identified, the mechanisms of action of many of them remain largely unknown. The aim of this study was to identify specific relationships between 14 factors required for cell differentiation and pattern formation by exploring their putative physical interactions in the cyanobacterium model Nostoc sp. PCC 7120 and by probing their evolutionary conservation and distribution across the cyanobacterial phylum. A bacterial two-hybrid assay indicated that 10 of the 14 factors studied here are engaged in more than one protein-protein interaction. The transcriptional regulator PatB was central in this network as it showed the highest number of binary interactions. A phylum-wide genomic survey of the distribution of these factors in cyanobacteria showed that they are all highly conserved in the genomes of heterocyst-forming strains, with the PatN protein being almost restricted to this clade. Interestingly, eight of the factors that were shown to be capable of protein interactions were identified as key elements in the evolutionary genomics analysis. These data suggest that a network of 12 proteins may play a crucial role in heterocyst development and patterning. Unraveling the physical and functional interactions between these factors during heterocyst development will certainly shed light on the mechanisms underlying pattern establishment in cyanobacteria.