Models of sequestration and receptor cross-talk for explaining multiple mutants in plant stem cell regulation

We present two models for the CLAVATA-WUSCHEL feedback network including two receptor pathways for WUSCHEL repression and differing only by the hypothesized mechanisms for the clavata1-1 non-null mutant. The first model is an implementation of the previously suggested interference mechanism. The other model assumes an unaltered binding between CLAVATA3 and the mutated CLAVATA1 but with a loss of propagated signal into the cell. We optimize the models using data from wild type and four single receptor mutant experiments and use data from two receptor double mutant experiments in a validation step. Both models are able to explain all seven phenotypes and in addition qualitatively predict CLAVATA3 perturbations. The two models for the clavata1-1 mutant differ in the direct mechanism of the mutant, but they also predict other differences in the dynamics of the stem cell regulating network. We show that the interference hypothesis leads to an abundance of receptors, while the loss-of-signal hypothesis leads to sequestration of CLAVATA3 and relies on degradation or internalization of the bound CLAVATA1 receptor.Using computational modeling, we show that an interference hypothesis and a more parsimonious loss-of-signal hypothesis for a clavata1 non-null mutant both lead to behaviors predicting wild type and six receptor mutant experiments. Although the two models have identical implementations of the unperturbed feedback network for stem cell regulation, we can point out model-predicted differences that may be resolved in future experiments.The development of animals and plants is dependent on undifferentiated stem cells residing in special locations called niches [1]. In a plant, stem cells are maintained in the shoot apical meristem (SAM) throughout its life, and the SAM is the source of all aerial parts of the plant [2,3].Spatial regions of different expression patterns and functions are found within the SAM. The central zone is located at the tip of the apex and consis