An Assumption of The Regulatory Function of Nf2-Amot Complex in Early Mammalian Embryos with A Computational Model

Abstract

The paper assumed that Nf2-Amot complex regulates the phosphorylation cascade so that each cell in the early mammalian embryo differentiates properly in silico. To confirm the validity of the assumption, it was necessary to verify whether Nf2-Amot complex has an impact on the resulting differentiation. The living embryo is unsuitable for the confirmation since the early mammalian embryo is too small to observe and too ethically sensitive to invade. In such cases, computational models can be used as experimental subjects for operations that cannot be applied to the living embryo. Previous models on the embryo, however, could not verify the assumption because they had not modeled Nf2-Amot complex, and they seldom modeled the Hippo signaling pathway. Therefore, the paper introduced a model of Nf2-Amot complex to the previous study that had modeled the Hippo signaling pathway. Testing the model under diverse conditions revealed that the existence of Nf2-Amot complex reproduces the ideal cell differentiation observed in the living embryo. In this sense, the validity of the model was confirmed. Furthermore, diverse cell-cell contacts that induce various concentrations of Nf2-Amot complex also resulted in ideal cell differentiation. These results suggested the correctness of the assumption in silico.