Singh, D. N. D. | Search bioRxiv

bioRxiv2026

decepentaplegic directs the wiring of female-differentiated fruitless sex peptide response-inducing neurons

Female reproductive success requires coordinated behavioural responses following mating. In Drosophila melanogaster, these responses are induced by male-derived sex-peptide (SP) and include reduced receptivity to further mating and increased oviposition. Although the neural pathways controlling these behaviours have been partially characterized, the developmental mechanisms that establish and maintain these circuits remain poorly understood. Using a genetic approach, we identified an EMS-induced mutant that retains eggs and fails to reduce receptivity following SP exposure. We mapped this mutation to the transcription termination zone after the polyA site of the dpp locus and show that this allele dppHB3 affects expression. Dpp/BMP signalling acts within SP response-inducing neurons (SPRINz) and is required for correct neuronal wiring in dppHB3 mutants. We further find that the SPRINZ-fru11/12 enhancer induces gene expression upon Dpp exposure. Also, female sexual differentiation trough the sex determination gene tra is required in SPRINz to display post-mating behaviours. Together, these findings suggest a new role for dpp in specifying neuronal connectivity in the context of sexual differentiation by the Drosophila canonical sex determination pathway to implement neuronal wiring for post-mating behaviours.

genetics↗

bioRxiv2024

Fungi activate Toll-1 dependent immune evasion to induce cell loss in the host brain

Fungi evolve within the host, ensuring their own nutrition and reproduction, at the expense of host health. They intervene in hosts brain function, to alter host behaviour and induce neurodegeneration. In humans, fungal infections are emerging as drivers of neuroinflammation, neurodegenerative diseases and psychiatric disorders. However, how fungi alter the host brain is unknown. Fungi trigger an innate immune response mediated by the Toll-1/TLR receptor, the adaptor MyD88 and the transcription factor Dif/NF{kappa}B, that induce the expression of antimicrobial peptides (AMPs). However, in the nervous system, Toll-1/TLR could also drive an alternative pathway involving the adaptor Sarm, which causes cell death instead. Sarm is the universal inhibitor of MyD88 and could drive immune evasion. The entomopathogenic fungus Beauveria bassiana is well-known to activate Toll-1 signalling in innate immunity in Drosophila. In fruit-flies, the adaptor Wek links Toll-1 to Sarm. Thus, here we asked whether B. bassiana could damage the Drosophila brain via Toll-1, Wek and Sarm. We show that exposure to B. bassiana reduced fly lifespan and impaired locomotion. B. bassiana entered the brain and induced the up-regulation of AMPs, as well as wek and sarm, within the brain. Exposure to B. bassiana caused neuronal and glial loss in the adult Drosophila brain. Importantly, RNAi knockdown of Toll-1, wek or sarm concomitantly with infection prevented B. bassiana induced cell loss. By contrast, over-expression of wek or sarm was sufficient to cause dopaminergic neuron loss in the absence of infection. These data show that B. bassiana caused cell loss in the host brain via Toll-1/Wek/Sarm signalling driving immune evasion. We conclude that pathogens can benefit from an innate immunity receptor to damage the host brain. A similar activation of Sarm downstream of TLRs in response to fungal infections could underlie psychiatric and neurodegenerative diseases in humans.

neuroscience↗