Most macromolecules found in cells are chiral (an object is chiral if it is distinguishable from its mirror image). However, chirality of cells has not been noticed until very recently. In our attempt to understand the mechanisms of left-right (LR) asymmetric development in Drosophila, we revealed that cells have intrinsic chirality in their structure.
Mechanisms of LR asymmetric development are evolutionarily diverged and remain elusive in invertebrates. Drosophila has various organs, such as the gut, testes, and male genitalia, which show stereotypic LR asymmetry. Our research focused on the LR asymmetric development of the embryonic gut that is first organ to show LR asymmetry during Drosophila development. The embryonic hindgut rotates counterclockwise 90 degree during its LR asymmetric morphogenesis. The active force driving this rotation originates from hindgut epithelium without any contribution of cell proliferation or apoptosis. Our three dimensional analysis of hindgut epithelium structure revealed that epithelial cells show chirality in their shape, which is the first demonstration of cell chirality in vivo. Our computer simulation analysis suggested that cell chirality drives the LR asymmetric rotation of the hindgut, so demonstrating the biological function of cell chirality for the first time. Similar cell chirality was found in other fly organs showing LR asymmetry, and its contributions to the LR asymmetric morphogenesis of these organs were similarly indicated.
To identify genes involved in LR asymmetric development, we have conducted genetic screens covering most of fly genome. We identified Myosin31DF (Myo31DF), encoding Drosophila Myosin ID, as mutants in which LR asymmetry becomes sinistral (mirror image of wild-type counterpart). These results suggest that the default state of handedness is sinistral in Drosophila, and the default handedness is reversed by Myo31DF in wild type. Interestingly, cell chirality also becomes mirror image in these mutants. Our mosaic analyses involving Myo31DF mutant revealed that cell chirality is intrinsically formed in individual cells.
Recently, cell chirality was reported in various vertebrate cultured cells, and these analyses suggested evolutionarily conservation of cell chirality. However, biological roles of cell chirality remain unknown in vertebrates. Thus, the Drosophila system may provide important insights into the functions of cell chirality and the genetic mechanisms of its formation.