(A) HetL, All3256 or All4303 PR domains organization. (B) Bacterial two hybrid assay between HetR and HetL paralogs. BTH101 strain was transformed with pKT25-hetR and pUT18C-all4303 or pUT18C-all3256, β-galactosidase activities were measured as described in section ‘Materials and methods’ and were expressed in Miller units. Strains producing the T18 and T25 served as negative control. Strains producing T18-Zip and T25-Zip served as positive control. Error bars indicate standard deviation. The characteristics of the fusion proteins used in this assay are indicated below: HetR-HetL: T25-HetR/T18-HetL; HetR-All4303: T25-HetR/T18-All4303; HetR-All3256: T25-HetR/T18-All3256. (C) Schematic model integrating HetL in the patterning system of Nostoc. R: HetR, L: HetL or HetL homolog, IM: inhibiting morphogen (Providing from the processing of PatX, PatS or HetN). Local activation/protection: once activated, HetR activates the transcription of hetR, hetL, patS/hetN. The HetR/HetL network is favored. HetL provides immunity against the inhibiting morphogens produced in situ or entering the cell. HetR is active, heterocyst develops. Long range inhibition: the diffusion of the morphogens from both sides of the heterocyst creates an inhibition gradient. In the HetR/Morphogen network, HetR is inactive and the concentration of HetL is below the protective threshold. Differentiation is inhibited.