Statistical validation verifies that enantiomorphic states of cell chirality are determinant dictating the left- or right-handed direction of the hindgut rotation in Drosophila

In the left-right (LR) asymmetric development of invertebrates, chirality of cells (cell chirality) plays crucial roles. Left- or right-handed structure of cells consequently directs the morphogenesis with corresponding LR asymmetry. In Drosophila, it has been suggested that cell chirality drives the LR-asymmetric development of various organs including the embryonic hindgut. However, this hypothesis is supported only by apparent concordance between these two events and by computer simulations connecting them [1-5]. Therefore, here, we mathematically evaluated the causal relationship between the cell chirality of the hindgut epithelial cells and the LR-directional rotation of the hindgut, which was previously postulated. Our logistic model obtained from various genetic backgrounds significantly explained the correlation between the enantiomorphic states of cell chirality and the LR directionality of hindgut rotation. This model also significantly explained the correlation between cell chirality stochastically formed in advance in each living embryo and the LR-directionality of the following rotation, suggesting the irrelevance of modes how cell chirality is formed. This analysis also showed that the cell chirality is not only sufficient but also required for the rotation. Considering the chronological order of these events, our study validated that cell chirality causally defines the LR asymmetry of the hindgut rotation.