Rational selection of morphological phenotypic traits to extract essential similarities in chemical perturbation in the ergosterol pathway.

Terbinafine, fluconazole, and amorolfine inhibit fungal ergosterol synthesis by acting on their target enzymes at different steps in the synthetic pathway, causing the accumulation of various intermediates. We found that the effects of these three in- hibitors on yeast morphology were different. The number of morphological parameters commonly altered by these drugs was only approximately 6% of the total. Using a rational strategy to find commonly changed parameters,we focused on hidden essential similarities in the phenotypes possibly due to decreased ergosterol levels. This resulted in higher apparent morphological similarity. Improvements in morphological similarity were observed even when canonical correlation analysis was used to select biologically meaningful morphological parameters related to gene function. In addition to changes in cell morphology, we also observed differences in the synergistic effects among the three inhibitors and in their fungicidal effects against pathogenic fungi possibly due to the accumulation of different intermediates. This study provided a comprehensive understanding of the properties of inhibitors acting in the same biosynthetic pathway.

Unveiling the cell dynamics during the final shape formation of the tarsus in Drosophila adult leg by live imaging.

Organisms display a remarkable diversity in their shapes. Although substantial progress has been made in unraveling the mechanisms that govern cell fate determination during development, the mechanisms by which fate-determined cells give rise to the final shapes of organisms remain largely unknown. This study describes in detail the process of the final shape formation of the tarsus, which is near the distal tip of the adult leg, during the pupal stage in Drosophila melanogaster. Days-long live imaging revealed unexpectedly complicated cellular dynamics. The epithelial cells transiently form the intriguing structure, which we named the Parthenon-like structure. The basal surface of the epithelial cells and localization of the basement membrane protein initially show a mesh-like structure and rapidly shrink into the membranous structure during the formation and disappearance of the Parthenon-like structure. Furthermore, macrophage-like cells are observed moving around actively in the Parthenon-like structure and engulfing epithelial cells. The findings in this research are expected to significantly contribute to our understanding of the mechanisms involved in shaping the final structure of the adult tarsus.