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An integrative approach for modeling and simulation of heterocyst pattern formation in cyanobacteria filaments.

Torres-Sánchez A, Gómez-Gardeñes J, Falo F - PLoS Comput. Biol. (2015)

Bottom Line: This framework allows us to formulate the essential dynamical ingredients of the genetic circuit of a single cyanobacterium into a set of differential equations describing the time evolution of the concentrations of the relevant molecular products.These two ingredients allow us to understand the principles by which heterocyst patterns can be generated and sustained.Finally, we discuss the validity and possible improvements of the model.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Física de la Materia Condensada, Universidad de Zaragoza, Zaragoza, Spain; Laboratori de Càlcul Numèric, Universitat de Politècnica de Catalunya, Barcelona, Spain.

ABSTRACT
Heterocyst differentiation in cyanobacteria filaments is one of the simplest examples of cellular differentiation and pattern formation in multicellular organisms. Despite of the many experimental studies addressing the evolution and sustainment of heterocyst patterns and the knowledge of the genetic circuit underlying the behavior of single cyanobacterium under nitrogen deprivation, there is still a theoretical gap connecting these two macroscopic and microscopic processes. As an attempt to shed light on this issue, here we explore heterocyst differentiation under the paradigm of systems biology. This framework allows us to formulate the essential dynamical ingredients of the genetic circuit of a single cyanobacterium into a set of differential equations describing the time evolution of the concentrations of the relevant molecular products. As a result, we are able to study the behavior of a single cyanobacterium under different external conditions, emulating nitrogen deprivation, and simulate the dynamics of cyanobacteria filaments by coupling their respective genetic circuits via molecular diffusion. These two ingredients allow us to understand the principles by which heterocyst patterns can be generated and sustained. In particular, our results point out that, by including both diffusion and noisy external conditions in the computational model, it is possible to reproduce the main features of the formation and sustainment of heterocyst patterns in cyanobacteria filaments as observed experimentally. Finally, we discuss the validity and possible improvements of the model.

No MeSH data available.


Related in: MedlinePlus

GS/GOGAT cycle.2-OG and cN indirectly interact through the GS/GOGAT cycle. Glutamine is transformed into glutamate by means of 2-OG through the 2-OG amidotransferase (GOGAT) while cN converts glutamate into glutamine through the glutamine synthetase (GS). The importance of the cycle in heterocyst differentiation is twofold. From one side, it constitutes the early one-cell sensor to nitrogen starvation: the absence of cN breaks the cycle down and 2-OG starts to accumulate, whose action leads to the cascade of processes that provoke the differentiation (see Fig. 1). Additionally, later during the differentiation, it processes the cN created by the heterocysts decreasing the levels of 2-OG. The latter is crucial for the formation of the heterocyst pattern (see Fig. 3).
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pcbi.1004129.g002: GS/GOGAT cycle.2-OG and cN indirectly interact through the GS/GOGAT cycle. Glutamine is transformed into glutamate by means of 2-OG through the 2-OG amidotransferase (GOGAT) while cN converts glutamate into glutamine through the glutamine synthetase (GS). The importance of the cycle in heterocyst differentiation is twofold. From one side, it constitutes the early one-cell sensor to nitrogen starvation: the absence of cN breaks the cycle down and 2-OG starts to accumulate, whose action leads to the cascade of processes that provoke the differentiation (see Fig. 1). Additionally, later during the differentiation, it processes the cN created by the heterocysts decreasing the levels of 2-OG. The latter is crucial for the formation of the heterocyst pattern (see Fig. 3).

Mentions: Rectangular boxes represent genes (ntcA, hetR and patS) while rounded boxes and circles represent transcription factors (NtcA, HetR and PatS) and smaller molecules (2-OG and cN) respectively. Normal-tipped and flat-tipped arrows stand for up-regulating and down-regulating processes respectively. Dashed lines stand for indirect or imperfectly understood interactions. The accumulation of 2-OG enhances the DNA-binding activity of NtcA, which in turn up-regulates the transcription of ntcA and hetR. HetR activates ntcA and hetR (composing the central NtcA-HetR autoregulatory loop), the inhibitor patS and other genes that lead to nitrogen fixation and the morphological changes involved in heterocyst differentiation. 2-OG and cN levels are linked through the GS/GOGAT cycle (see Fig. 2).


An integrative approach for modeling and simulation of heterocyst pattern formation in cyanobacteria filaments.

Torres-Sánchez A, Gómez-Gardeñes J, Falo F - PLoS Comput. Biol. (2015)

GS/GOGAT cycle.2-OG and cN indirectly interact through the GS/GOGAT cycle. Glutamine is transformed into glutamate by means of 2-OG through the 2-OG amidotransferase (GOGAT) while cN converts glutamate into glutamine through the glutamine synthetase (GS). The importance of the cycle in heterocyst differentiation is twofold. From one side, it constitutes the early one-cell sensor to nitrogen starvation: the absence of cN breaks the cycle down and 2-OG starts to accumulate, whose action leads to the cascade of processes that provoke the differentiation (see Fig. 1). Additionally, later during the differentiation, it processes the cN created by the heterocysts decreasing the levels of 2-OG. The latter is crucial for the formation of the heterocyst pattern (see Fig. 3).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376521&req=5

pcbi.1004129.g002: GS/GOGAT cycle.2-OG and cN indirectly interact through the GS/GOGAT cycle. Glutamine is transformed into glutamate by means of 2-OG through the 2-OG amidotransferase (GOGAT) while cN converts glutamate into glutamine through the glutamine synthetase (GS). The importance of the cycle in heterocyst differentiation is twofold. From one side, it constitutes the early one-cell sensor to nitrogen starvation: the absence of cN breaks the cycle down and 2-OG starts to accumulate, whose action leads to the cascade of processes that provoke the differentiation (see Fig. 1). Additionally, later during the differentiation, it processes the cN created by the heterocysts decreasing the levels of 2-OG. The latter is crucial for the formation of the heterocyst pattern (see Fig. 3).
Mentions: Rectangular boxes represent genes (ntcA, hetR and patS) while rounded boxes and circles represent transcription factors (NtcA, HetR and PatS) and smaller molecules (2-OG and cN) respectively. Normal-tipped and flat-tipped arrows stand for up-regulating and down-regulating processes respectively. Dashed lines stand for indirect or imperfectly understood interactions. The accumulation of 2-OG enhances the DNA-binding activity of NtcA, which in turn up-regulates the transcription of ntcA and hetR. HetR activates ntcA and hetR (composing the central NtcA-HetR autoregulatory loop), the inhibitor patS and other genes that lead to nitrogen fixation and the morphological changes involved in heterocyst differentiation. 2-OG and cN levels are linked through the GS/GOGAT cycle (see Fig. 2).

Bottom Line: This framework allows us to formulate the essential dynamical ingredients of the genetic circuit of a single cyanobacterium into a set of differential equations describing the time evolution of the concentrations of the relevant molecular products.These two ingredients allow us to understand the principles by which heterocyst patterns can be generated and sustained.Finally, we discuss the validity and possible improvements of the model.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Física de la Materia Condensada, Universidad de Zaragoza, Zaragoza, Spain; Laboratori de Càlcul Numèric, Universitat de Politècnica de Catalunya, Barcelona, Spain.

ABSTRACT
Heterocyst differentiation in cyanobacteria filaments is one of the simplest examples of cellular differentiation and pattern formation in multicellular organisms. Despite of the many experimental studies addressing the evolution and sustainment of heterocyst patterns and the knowledge of the genetic circuit underlying the behavior of single cyanobacterium under nitrogen deprivation, there is still a theoretical gap connecting these two macroscopic and microscopic processes. As an attempt to shed light on this issue, here we explore heterocyst differentiation under the paradigm of systems biology. This framework allows us to formulate the essential dynamical ingredients of the genetic circuit of a single cyanobacterium into a set of differential equations describing the time evolution of the concentrations of the relevant molecular products. As a result, we are able to study the behavior of a single cyanobacterium under different external conditions, emulating nitrogen deprivation, and simulate the dynamics of cyanobacteria filaments by coupling their respective genetic circuits via molecular diffusion. These two ingredients allow us to understand the principles by which heterocyst patterns can be generated and sustained. In particular, our results point out that, by including both diffusion and noisy external conditions in the computational model, it is possible to reproduce the main features of the formation and sustainment of heterocyst patterns in cyanobacteria filaments as observed experimentally. Finally, we discuss the validity and possible improvements of the model.

No MeSH data available.


Related in: MedlinePlus