Left-right asymmetry in Drosophila

In metazoans, the internal and external organs often show a directional left-right (LR) asymmetric morphology, which is determined genetically. The mechanisms underlying the formation of the LR axis have been extensively studied in vertebrates. However, recent studies revealed that the mechanisms responsible for symmetry breaking may have evolutionarily diverged even among vertebrates. Moreover, several aspects of the LR asymmetric development that are unique to invertebrates have been revealed. This indicates that there must be some unknown mechanisms of LR asymmetric development in these species. However, cues braking LR symmetry in invertebrates and subsequent mechanisms of LR development are poorly understood.

To uncover these novel genetic and molecular mechanisms of LR asymmetric development, we have been studying the LR asymmetric development in Drosophila. In Drosophila, several organs, including the gut, adult brain, spermiduct, and genital plate, show LR asymmetry. Among them, the embryonic gut is the first organ that develops LR asymmetry during embryogenesis. The LR asymmetric structure of the embryonic gut is highly stereotypic, just like human internal organs. Therefore, the embryonic gut is suitable for studying the mechanisms of LR asymmetric development.

Notch signaling

During development of metazoans, cells communicate using limited set of signal transduction pathways. Notch signaling is one of these pathways that is characterized by the nature of its ligands (most of them are transmembrane proteins, which means signal activation upon direct cell-cell contact) and its signal transduction system (Notch receptor intracellular domain, called NICD, directly activates transcription of downstream genes). Notch signaling is highly conserved among metazoans and involved in many cell processes, such as proliferation, differentiation, and apoptosis. Although many components of Notch signaling have been identified, many aspects of Notch regulation are still ambiguous.