Under combined nitrogen starvation, Anabaena perceives the presence of N2 and launches in response a developmental program leading to heterocysts: microoxic cells devoted to atmospheric nitrogen fixation. Heterocysts are formed at a semi-regular pattern that follows the Turing-model rules: in the developing cell, a transcriptional regulator (HetR) activates a specific transcriptional program that includes the expression of its own inhibitors. The diffusion of these inhibitory morphogens along the filament ensures pattern establishment. This initiation step is followed by a morphological differentiation which leads to the mature heterocyst and only at this point the nitrogenase encoding genes are expressed and N2 is fixed. We study the molecular mechanisms that allow the developing cell to sense the signal and to express the genes specific to each step of the process. How the transcriptional regulators involved act to orchestrate this temporal and cell specific transcription program? What are the sigma factors involved and how is their action regulated? How are the morphogens maturated and how do they diffuse along the filament? What is the distribution and evolution of the heterocyst-specific genes across the cyanobacterial phylum? Those are the main questions we aim to answer by combining genetics, biochemistry and genomics approaches.
Legend FigA : The three main steps of cell differentiation in Anabaena: NtcA, HetR and PatB are transcriptional regulator controlling the heterocyst-specific transcriptional program. HetP, HetZ and PatU3 are involved int the commitment step. The activity of HetR in the vegetative cells is inhibited by diffusible morphogens issued from PatS, PatX and HetN. The yellow arrows indicate heterocysts.
Legend FigB : Self-organized patterning in Anabaena:
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
R: HetR, L: HetL or HetL homolog, IM: inhibiting morphogen (Providing from the processing of PatX, PatS or HetN).