Delta/Notch signaling in glia maintains motor nerve barrier function and synaptic transmission by controlling matrix metalloproteinase expression.

While the role of barrier function in establishing a protective, nutrient-rich, and ionically balanced environment for neurons has been appreciated for some time, little is known about how signaling cues originating in barrier-forming cells participate in maintaining barrier function and influence synaptic activity. We have identified Delta/Notch signaling in subperineurial glia (SPG), a crucial glial type for motor axon ensheathment and the blood-brain barrier, to be essential for controlling the expression of matrix metalloproteinase 1 (Mmp1), a major regulator of the extracellular matrix (ECM). Our genetic analysis indicates that Delta/Notch signaling in SPG exerts an inhibitory control on Mmp1 expression.

Gut cytokines modulate olfaction through metabolic reprogramming of glia.

Infection-induced aversion against enteropathogens is a conserved sickness behaviour that can promote host survival. The aetiology of this behaviour remains poorly understood, but studies in Drosophila have linked olfactory and gustatory perception to avoidance behaviours against toxic microorganisms. Whether and how enteric infections directly influence sensory perception to induce or modulate such behaviours remains unknown.

Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal permeability and survival in Drosophila.

Exposure to genotoxic stress by environmental agents or treatments, such as radiation therapy, can diminish healthspan and accelerate aging. We have developed a Drosophila melanogaster model to study the molecular effects of radiation-induced damage and repair. Utilizing a quantitative intestinal permeability assay, we performed an unbiased GWAS screen (using 156 strains from the Drosophila Genetic Reference Panel) to search for natural genetic variants that regulate radiation-induced gut permeability in adult D.

A Neuron-Glial Trans-Signaling Cascade Mediates LRRK2-Induced Neurodegeneration.

Pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2) induce an age-dependent loss of dopaminergic (DA) neurons. We have identified Furin 1, a pro-protein convertase, as a translational target of LRRK2 in DA neurons. Transgenic knockdown of Furin1 or its substrate the bone morphogenic protein (BMP) ligand glass bottom boat (Gbb) protects against LRRK2-induced loss of DA neurons.

Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge.

The Drosophila defense against pathogens largely relies on the activation of two signaling pathways: immune deficiency (IMD) and Toll. The IMD pathway is triggered mainly by Gram-negative bacteria, whereas the Toll pathway responds predominantly to Gram-positive bacteria and fungi. The activation of these pathways leads to the rapid induction of numerous NF-κB-induced immune response genes, including antimicrobial peptide genes.