Limits...
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.


A map of links for each top topology to the decomposed functions for VPC patterning.(Left columns) Top topologies ranking within the top 5 for each S2 are listed. Both cases of the “AND” rule and the “AND & Additive” rule are included. (Middle column) The S2 column shows the S2 levels at which the topologies performed the patterning robustly. L, low level; M, medium level; H, high level. (Right columns) For each topology (each row), its links are listed in different columns according to their functions. It should be noted that among these functions, inducing 2° fate in 1° cell and 1° fate in 2° cell (in red color) have adverse effects on the topologies’ performance of patterning. The numbers in parentheses indicate the sequential order of the functions for positive regulation. The same number means the functions have no causal or sequential relationship.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4482679&req=5

pone.0131397.g005: A map of links for each top topology to the decomposed functions for VPC patterning.(Left columns) Top topologies ranking within the top 5 for each S2 are listed. Both cases of the “AND” rule and the “AND & Additive” rule are included. (Middle column) The S2 column shows the S2 levels at which the topologies performed the patterning robustly. L, low level; M, medium level; H, high level. (Right columns) For each topology (each row), its links are listed in different columns according to their functions. It should be noted that among these functions, inducing 2° fate in 1° cell and 1° fate in 2° cell (in red color) have adverse effects on the topologies’ performance of patterning. The numbers in parentheses indicate the sequential order of the functions for positive regulation. The same number means the functions have no causal or sequential relationship.

Mentions: Although top topologies share some common patterning strategies, they employ different links to implement the strategies. Fig 5 shows how different top topologies employ distinct links to implement modular functions that contribute together to the patterning. Except for the links 7P and 8P that mean positive regulation by nodes 1° and 2° themselves, all links can be assigned one or two of the following six functions: inducing the 1° fate in the 1° cell, inducing the 2° fate in the 2° cells, inducing the 1° fate in the 2° cells, inducing the 2° fate in the 1° cell, inhibiting the 1° fate in the 2° cells, inhibiting the 2° fate in the 1° cell. With distinct implementation of each component function, the integrated VPC patterning program can be achieved by various combinations of different links.


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

Ping X, Tang C - PLoS ONE (2015)

A map of links for each top topology to the decomposed functions for VPC patterning.(Left columns) Top topologies ranking within the top 5 for each S2 are listed. Both cases of the “AND” rule and the “AND & Additive” rule are included. (Middle column) The S2 column shows the S2 levels at which the topologies performed the patterning robustly. L, low level; M, medium level; H, high level. (Right columns) For each topology (each row), its links are listed in different columns according to their functions. It should be noted that among these functions, inducing 2° fate in 1° cell and 1° fate in 2° cell (in red color) have adverse effects on the topologies’ performance of patterning. The numbers in parentheses indicate the sequential order of the functions for positive regulation. The same number means the functions have no causal or sequential relationship.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131397.g005: A map of links for each top topology to the decomposed functions for VPC patterning.(Left columns) Top topologies ranking within the top 5 for each S2 are listed. Both cases of the “AND” rule and the “AND & Additive” rule are included. (Middle column) The S2 column shows the S2 levels at which the topologies performed the patterning robustly. L, low level; M, medium level; H, high level. (Right columns) For each topology (each row), its links are listed in different columns according to their functions. It should be noted that among these functions, inducing 2° fate in 1° cell and 1° fate in 2° cell (in red color) have adverse effects on the topologies’ performance of patterning. The numbers in parentheses indicate the sequential order of the functions for positive regulation. The same number means the functions have no causal or sequential relationship.
Mentions: Although top topologies share some common patterning strategies, they employ different links to implement the strategies. Fig 5 shows how different top topologies employ distinct links to implement modular functions that contribute together to the patterning. Except for the links 7P and 8P that mean positive regulation by nodes 1° and 2° themselves, all links can be assigned one or two of the following six functions: inducing the 1° fate in the 1° cell, inducing the 2° fate in the 2° cells, inducing the 1° fate in the 2° cells, inducing the 2° fate in the 1° cell, inhibiting the 1° fate in the 2° cells, inhibiting the 2° fate in the 1° cell. With distinct implementation of each component function, the integrated VPC patterning program can be achieved by various combinations of different links.

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.