PatU3 plays a central role in coordinating cell division and differentiation in pattern formation of filamentous cyanobacterium Nostoc sp. PCC 7120

Spatial periodic signal for cell differentiation in some multicellular organisms is generated according to Turing's principle for pattern formation. How a dividing cell responds to the signal of differentiation is addressed with the filamentous cyanobacterium Nostoc sp. PCC 7120, which forms the patterned distribution of heterocysts. We show that differentiation of a dividing cell was delayed until its division was completed and only one daughter cell became heterocyst. A mutant of patU3, which encodes an inhibitor of heterocyst formation, showed no such delay and formed heterocyst pairs from the daughter cells of cell division or dumbbell-shaped heterocysts from the cells undergoing cytokinesis. The patA mutant, which forms heterocysts only at the filament ends, restored intercalary heterocysts by a single nucleotide mutation of patU3, and double mutants of patU3/patA and patU3/hetF had the phenotypes of the patU3 mutant. We provide evidence that HetF, which can degrade PatU3, is recruited to cell divisome through its C-terminal domain. A HetF mutant with its N-terminal peptidase domain but lacking the C-terminal domain could not prevent the formation of heterocyst pairs, suggesting that the divisome recruitment of HetF is needed to sequester HetF for the delay of differentiation in dividing cells. Our study demonstrates that PatU3 plays a key role in cell-division coupled control of differentiation.

Automated summary

Spatial periodic signal based on Turing's principle is used to simulate cell differentiation in multicellular organisms. In the filamentous cyanobacterium Nostoc sp. PCC 7120, a dividing cell delays differentiation until completion of division, resulting in only one daughter cell becoming heterocyst. Mutants of patU3, an inhibitor of heterocyst formation, do not show this delay and form heterocyst pairs or dumbbell-shaped heterocysts from dividing cells or cells undergoing cytokinesis. PatA mutant restores intercalary heterocysts by a single nucleotide mutation of patU3, and double mutants of patU3/patA and patU3/hetF exhibit patU3 mutant phenotypes. HetF, which degrades PatU3, is recruited to the cell divisome through its C-terminal domain. A HetF mutant lacking the C-terminal domain fails to prevent heterocyst pair formation, indicating the importance of divisome recruitment of HetF for delaying differentiation in dividing cells. This study highlights the key role of PatU3 in cell-division coupled control of differentiation.