Abstract
BackgroundThere are recent experimental reports on the cross-regulation between molecules involved in the control of the cell cycle and the differentiation of the vulval precursor cells (VPCs) of Caenorhabditis elegans. Such discoveries provide novel clues on how the molecular mechanisms involved in the cell cycle and cell differentiation processes are coordinated during vulval development. Dynamic computational models are helpful to understand the integrated regulatory mechanisms affecting these cellular processes.ResultsHere we propose a simplified model of the regulatory network that includes sufficient molecules involved in the control of both the cell cycle and cell differentiation in the C. elegans vulva to recover their dynamic behavior. We first infer both the topology and the update rules of the cell cycle module from an expected time series. Next, we use a symbolic algorithmic approach to find which interactions must be included in the regulatory network. Finally, we use a continuous-time version of the update rules for the cell cycle module to validate the cyclic behavior of the network, as well as to rule out the presence of potential artifacts due to the synchronous updating of the discrete model. We analyze the dynamical behavior of the model for the wild type and several mutants, finding that most of the results are consistent with published experimental results.ConclusionsOur model shows that the regulation of Notch signaling by the cell cycle preserves the potential of the VPCs and the three vulval fates to differentiate and de-differentiate, allowing them to remain completely responsive to the concentration of LIN-3 and lateral signal in the extracellular microenvironment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0498-z) contains supplementary material, which is available to authorized users.
Highlights
There are recent experimental reports on the cross-regulation between molecules involved in the control of the cell cycle and the differentiation of the vulval precursor cells (VPCs) of Caenorhabditis elegans
Attractors D, E, F and G correspond to the secondary vulval fate which is characterized by LIN-12i activity
Our model recovers the stable patterns of activation of the considered molecular components under wild type and mutant conditions, replicating those patterns encountered on actual cells during vulval development in C. elegans
Summary
There are recent experimental reports on the cross-regulation between molecules involved in the control of the cell cycle and the differentiation of the vulval precursor cells (VPCs) of Caenorhabditis elegans. Such discoveries provide novel clues on how the molecular mechanisms involved in the cell cycle and cell differentiation processes are coordinated during vulval development. The vulva has two main biological functions, namely, copulation and egg laying This organ is formed by seven epithelial rings connecting the uterus with the ventral hypodermis, forming a path from the interior of the uterus to the external environment. Most of these rings are formed by a single tetranucleated syncytium, the exceptions being the binucleated syncytium ring vulD, as well as the vulB1 and vulB2 rings that contain two half-ring binucleated syncytia each [6]
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