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An Atlas of Network Topologies Reveals Design Principles for Caenorhabditis elegans Vulval Precursor Cell Fate Patterning.

Ping X, Tang C - PLoS ONE (2015)

Bottom Line: We show that the topology derived by mapping currently known biochemical pathways to our model matches one of our identified functional topologies.Furthermore, our robustness analysis predicts a possible missing link related to the lateral antagonism strategy.Overall, we provide a theoretical atlas of all possible functional networks in varying environments, which may guide novel discoveries of the biological interactions in vulval development of Caenorhabditis elegans and related species.

View Article: PubMed Central - PubMed

Affiliation: Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.

ABSTRACT
The vulval precursor cell (VPC) fate patterning in Caenorhabditis elegans is a classic model experimental system for cell fate determination and patterning in development. Despite its apparent simplicity (six neighboring cells arranged in one dimension) and many experimental and computational efforts, the patterning strategy and mechanism remain controversial due to incomplete knowledge of the complex biology. Here, we carry out a comprehensive computational analysis and obtain a reservoir of all possible network topologies that are capable of VPC fate patterning under the simulation of various biological environments and regulatory rules. We identify three patterning strategies: sequential induction, morphogen gradient and lateral antagonism, depending on the features of the signal secreted from the anchor cell. The strategy of lateral antagonism, which has not been reported in previous studies of VPC patterning, employs a mutual inhibition of the 2° cell fate in neighboring cells. Robust topologies are built upon minimal topologies with basic patterning strategies and have more flexible and redundant implementations of modular functions. By simulated mutation, we find that all three strategies can reproduce experimental error patterns of mutants. We show that the topology derived by mapping currently known biochemical pathways to our model matches one of our identified functional topologies. Furthermore, our robustness analysis predicts a possible missing link related to the lateral antagonism strategy. Overall, we provide a theoretical atlas of all possible functional networks in varying environments, which may guide novel discoveries of the biological interactions in vulval development of Caenorhabditis elegans and related species.

No MeSH data available.


Summary of the topologies and parameter sets that achieve the patterning function.(A, B) Number of topologies with Q ≥ 0.1 and Q ≥ 0.01 for different S2 values with “AND” rule (A) and “Combined AND & Additive” rule (B). (C, D) For different S2 values, the distribution of parameter sets for functional topologies that contain module 1P-5P or 1P-2P with “AND” rule (C) and “Combined AND & Additive” rule (D). In the legend of C and D, “1P-5P”, “1P-2P”, “Both”, and “None” indicate the parameter sets on which there are only topologies with 1P-5P, only topologies with 1P-2P, both topologies with 1P-5P and topologies with 1P-2P, and none of the topologies with 1P-5P or 1P-2P.
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pone.0131397.g002: Summary of the topologies and parameter sets that achieve the patterning function.(A, B) Number of topologies with Q ≥ 0.1 and Q ≥ 0.01 for different S2 values with “AND” rule (A) and “Combined AND & Additive” rule (B). (C, D) For different S2 values, the distribution of parameter sets for functional topologies that contain module 1P-5P or 1P-2P with “AND” rule (C) and “Combined AND & Additive” rule (D). In the legend of C and D, “1P-5P”, “1P-2P”, “Both”, and “None” indicate the parameter sets on which there are only topologies with 1P-5P, only topologies with 1P-2P, both topologies with 1P-5P and topologies with 1P-2P, and none of the topologies with 1P-5P or 1P-2P.

Mentions: We searched the topologies of networks that robustly achieve VPC patterning for different values of the signal input to the 2° cells, while fixing the source input to the 1° cell (see Materials and Methods). S1 and S2 Tables list all robust topologies (Q ≥ 0.1) for different S2 with “AND” and “Combined AND and Additive” rules, respectively. Only a small proportion of topologies have Q ≥ 0.1 or Q ≥ 0.01 (Fig 2A and 2B). For example, for S2 = 0 and with the “AND” rule, there are only 37 topologies (from a total of 59,049) with Q >0.1 and 113 topologies with Q >0.01. This result agrees with previous studies in other systems [5,6]: function constrains the topologies of networks.


An Atlas of Network Topologies Reveals Design Principles for Caenorhabditis elegans Vulval Precursor Cell Fate Patterning.

Ping X, Tang C - PLoS ONE (2015)

Summary of the topologies and parameter sets that achieve the patterning function.(A, B) Number of topologies with Q ≥ 0.1 and Q ≥ 0.01 for different S2 values with “AND” rule (A) and “Combined AND & Additive” rule (B). (C, D) For different S2 values, the distribution of parameter sets for functional topologies that contain module 1P-5P or 1P-2P with “AND” rule (C) and “Combined AND & Additive” rule (D). In the legend of C and D, “1P-5P”, “1P-2P”, “Both”, and “None” indicate the parameter sets on which there are only topologies with 1P-5P, only topologies with 1P-2P, both topologies with 1P-5P and topologies with 1P-2P, and none of the topologies with 1P-5P or 1P-2P.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482679&req=5

pone.0131397.g002: Summary of the topologies and parameter sets that achieve the patterning function.(A, B) Number of topologies with Q ≥ 0.1 and Q ≥ 0.01 for different S2 values with “AND” rule (A) and “Combined AND & Additive” rule (B). (C, D) For different S2 values, the distribution of parameter sets for functional topologies that contain module 1P-5P or 1P-2P with “AND” rule (C) and “Combined AND & Additive” rule (D). In the legend of C and D, “1P-5P”, “1P-2P”, “Both”, and “None” indicate the parameter sets on which there are only topologies with 1P-5P, only topologies with 1P-2P, both topologies with 1P-5P and topologies with 1P-2P, and none of the topologies with 1P-5P or 1P-2P.
Mentions: We searched the topologies of networks that robustly achieve VPC patterning for different values of the signal input to the 2° cells, while fixing the source input to the 1° cell (see Materials and Methods). S1 and S2 Tables list all robust topologies (Q ≥ 0.1) for different S2 with “AND” and “Combined AND and Additive” rules, respectively. Only a small proportion of topologies have Q ≥ 0.1 or Q ≥ 0.01 (Fig 2A and 2B). For example, for S2 = 0 and with the “AND” rule, there are only 37 topologies (from a total of 59,049) with Q >0.1 and 113 topologies with Q >0.01. This result agrees with previous studies in other systems [5,6]: function constrains the topologies of networks.

Bottom Line: We show that the topology derived by mapping currently known biochemical pathways to our model matches one of our identified functional topologies.Furthermore, our robustness analysis predicts a possible missing link related to the lateral antagonism strategy.Overall, we provide a theoretical atlas of all possible functional networks in varying environments, which may guide novel discoveries of the biological interactions in vulval development of Caenorhabditis elegans and related species.

View Article: PubMed Central - PubMed

Affiliation: Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.

ABSTRACT
The vulval precursor cell (VPC) fate patterning in Caenorhabditis elegans is a classic model experimental system for cell fate determination and patterning in development. Despite its apparent simplicity (six neighboring cells arranged in one dimension) and many experimental and computational efforts, the patterning strategy and mechanism remain controversial due to incomplete knowledge of the complex biology. Here, we carry out a comprehensive computational analysis and obtain a reservoir of all possible network topologies that are capable of VPC fate patterning under the simulation of various biological environments and regulatory rules. We identify three patterning strategies: sequential induction, morphogen gradient and lateral antagonism, depending on the features of the signal secreted from the anchor cell. The strategy of lateral antagonism, which has not been reported in previous studies of VPC patterning, employs a mutual inhibition of the 2° cell fate in neighboring cells. Robust topologies are built upon minimal topologies with basic patterning strategies and have more flexible and redundant implementations of modular functions. By simulated mutation, we find that all three strategies can reproduce experimental error patterns of mutants. We show that the topology derived by mapping currently known biochemical pathways to our model matches one of our identified functional topologies. Furthermore, our robustness analysis predicts a possible missing link related to the lateral antagonism strategy. Overall, we provide a theoretical atlas of all possible functional networks in varying environments, which may guide novel discoveries of the biological interactions in vulval development of Caenorhabditis elegans and related species.

No MeSH data available.