Role of mitochondrial dynamics and function in Drosophila embryo morphogenesis

Abstract

Mitochondria, in addition to their well-known function of ATP synthesis, are also involved in a wide variety of cellular processes, such as apoptosis, calcium homeostasis and signalling. Mitochondria are structured by dedicated fusion and fission machinery that consists of well characterized GTPase proteins. The mitochondrial morphology is modified based on cell type and physiological requirements and is linked with a wide range of signalling pathways. Embryogenesis involves complex cascades of signalling that occur at specific milestones of the development. Hints from the literature suggest a temporal regulation of mitochondrial function and localization in ascidian and mammalian embryos. Mislocalization and deregulation of mitochondrial structure lead to cellular and embryonic lethality. However, a systematic analysis of mitochondrial shape and localization with respect to functional regulation and signalling during embryogenesis has not been carried out so far. We characterized mitochondria in early Drosophila embryogenesis using mitochondrially localized GFP and found that mitochondria are small and dispersed around nuclei in syncytial, cellular blastoderm, and gastrulating embryos. Mitochondria are basally enriched during syncytial stage and are actively re-distributed to the apical side during cellularization. Apical migration of mitochondria is specifically enhanced in the ventral furrow cells during gastrulation. This re-localization of mitochondria is microtubule dependent. This apical redistribution of mitochondria is abolished in embryos mutant for mitochondrial fission protein Drp1. Myosin II levels are reduced in drp1 mutant embryos and the cells formed during cellularization in embryos are shorter and have wider contractile rings at their basal regions. The misaligned ventral furrow cells also have lowered Myosin II accumulation at their apical regions in drp1 mutant embryos. This is likely due to reduced levels of reactive oxygen species (ROS) in these embryos. We find that apical mitochondrial transport in ventral furrow cells is regulated by the Toll-Dorsal pathway. Upregulation of Dorsal enhances the ventral signalling and apical accumulation of mitochondria whereas fog loss of function shows reduced mitochondrial apical transport in the ventral furrow cells. Thus, we demonstrate that mitochondrial localization is regulated by the Toll-Dorsal pathway and propose that their function is essential for functioning of Toll-Dorsal pathway. We are further examining the functional role of mitochondria in regulation of this pathway.