Statistical Validation Verifies That Enantiomorphic States of Chiral Cells Are Determinant Dictating the Left- or Right-Handed Direction of the Hindgut Rotation in Drosophila

In the left-right (LR) asymmetric development of invertebrates, cell chirality is crucial. A left- or right-handed cell structure directs morphogenesis with corresponding LR-asymmetry. In Drosophila, cell chirality is thought to drive the LR-asymmetric development of the embryonic hindgut and other organs. This hypothesis is supported only by an apparent concordance between the LR-directionality of cell chirality and hindgut rotation and by computer simulations that connect the two events. In this article, we mathematically evaluated the causal relationship between the chirality of the hindgut epithelial cells and the LR-direction of hindgut rotation. Our logistic model, drawn from several Drosophila genotypes, significantly explained the correlation between the enantiomorphic (sinistral or dextral) state of chiral cells and the LR-directionality of hindgut rotation-even in individual live mutant embryos with stochastically determined cell chirality and randomized hindgut rotation, suggesting that the mechanism by which cell chirality forms is irrelevant to the direction of hindgut rotation. Thus, our analysis showed that cell chirality, which forms before hindgut rotation, is both sufficient and required for the subsequent rotation, validating the hypothesis that cell chirality causally defines the LR-directionality of hindgut rotation.