Loss of function of phosphatidylserine synthase causes muscle atrophy in Drosophila.

Maintenance of appropriate muscle mass is crucial for physical activity and metabolism. Aging and various pathological conditions can cause sarcopenia, a condition characterized by muscle mass decline. Although sarcopenia has been actively studied, the mechanisms underlying muscle atrophy are not well understood. Thus, we aimed to investigate the role of Phosphatidylserine synthase (Pss) in muscle development and homeostasis in Drosophila. The results showed that muscle-specific Pss knockdown decreased exercise capacity and produced sarcopenic phenotypes. In addition, it increased the apoptosis rate because of the elevated reactive oxygen species production resulting from mitochondrial dysfunction. Moreover, the autophagy rate increased due to increased FoxO activity caused by reduced Akt activity. Collectively, these findings demonstrate that enhanced apoptosis and autophagy rates resulting from muscle-specific Pss knockdown jointly contribute to sarcopenia development, highlighting the key role of the PSS pathway in muscle health.

The CNS midline cells and Egfr signaling genes are required for establishment of the RP2 motoneuron lineage in the Drosophila central nervous system.

It is well established that CNS midline cells are essential for the identity determination, division, and differentiation of neurons and glia in the Drosophila CNS. However, it is not clear whether CNS midline cells control the establishment and differentiation of the well-known RP2 motoneuron lineage. The present study showed by using several RP2 lineage markers that CNS midline cells and Egfr signaling genes are required for identity determination and formation of precursors of the RP2 motoneurons. Overexpression and ectopic expression of sim and components of the EGFR signaling pathway in the ventral neuroectoderm induced the formation of extra RP2s and their sibling cells by activating EGFR signaling. We demonstrated that CNS midline cells and Egfr signaling genes play essential roles in the establishment of the RP2 motoneuron lineage.

Dpp represses eagle expression at short-range, but can repress its expression at a long-range via EGFR signal repression.

Nervous system development takes place after positional information has been established along the dorsal-ventral (D/V) axis. The initial subdivision provided by a gradient of nuclear dorsal protein is maintained by the zygotic genes expressed along the D/V axis. In this study, an investigation was conducted to determine the range of Dpp function in repressing the expression of eagle (eg) that is present in intermediate neuroblasts defective (ind) and muscle specific homeobox (msh) gene domain. eg is expressed in neuroblast (NB) 2-4, 3-3 and 6-4 of the msh domain, and NB7-3 of the ind domain at the embryonic stage 11. In decapentaplegic (dpp) loss-of-function mutant embryos, eg was ectopically expressed in the dorsal region, while in dpp gain-of-function mutants produced by sog or sca-GAL4/UAS-dpp, eg was repressed by Dpp. It is worthy of note that Dpp produced from sim;;dpp embryos showed that Dpp could function at long range. However, Dpp produced from en-GAL4/UAS-dpp or wg-GAL4/UAS-dpp primarily acted at short-range. This result demonstrated that this discrepancy seems to be due to the repression of Dpp to EGFR signaling in sim;;dpp embryos. Taken together, these results suggest that Dpp signaling works at short-range, but can function indirectly at long-range by way of repression of EGFR signaling during embryonic neurogenesis.

The hierarchical relationship among the spitz/Egfr signaling genes in cell fate determination in the Drosophila ventral neuroectoderm.

The spitz class and Egfr signaling (spi/Egfr) genes are required for the proper establishment of cell fate in the Drosophila ventral neuroectoderm. We investigated the role of the central nervous system (CNS) midline cells, and the hierarchical relationship among the spi/Egfr genes, in this process by analyzing the spatial and temporal expression of several of the genes in selected spi/Egfr mutants. Our analysis showed that expression of all the spi/Egfr genes is severely reduced in the single-minded (sim) mutant, and ectopically induced in en-Gal4/UAS-sim embryos. This result indicates that sim acts upstream of all the other spi/Egfr genes. The CNS midline cells regulate rhomboid (rho) expression in the ventral neuroectoderm and activate the EGFR signaling pathway. We also found that argos (aos) and orthodenticle (otd) act downstream of pointed (pnt), and that aos represses expression of otd in the lateral neuroectoderm to establish differential cell fates in the ventral neuroectoderm. Our findings suggest the following hierarchical relationship among the spi/Egfr genes: [see text].