Dscam1 overexpression impairs the function of the gut nervous system in Drosophila

Abstract

Background: Down syndrome (DS) patients have a 100-fold increase in the risk of Hirschsprung syndrome of the colon and rectum (HSCR), a lack of enteric neurons in the colon. The leading DS candidate gene is trisomy of the Down syndrome cell adhesion molecule (DSCAM).Results: We find that Dscam1 protein is expressed in the Drosophila enteric/ stomatogastric nervous system (SNS). Axonal Dscam1 phenotypes can be rescued equally by diverse isoforms. Overexpression of Dscam1 resulted in frontal and hindgut nerve overgrowth. Expression of dominant negative Dscam1-ΔC led to a truncated frontal nerve and increased branching of the hindgut nerve. Larval locomotion is influenced by feeding state, and we found that the average speed of larvae with Dscam1 SNS expression was reduced, whereas overexpression of Dscam1-ΔC significantly increased the speed. Dscam1 overexpression reduced the efficiency of food clearance from the larval gut. Conclusion: Our work demonstrates that overexpression of Dscam1 can perturb gut function in a model system.

Memory consolidation in honey bees is enhanced by down-regulation of Down syndrome cell adhesion molecule and changes its alternative splicing

“…Our finding that Dscam splicing changes upon learning further supports that the Dscam splicing pattern is not fixed and can change on demand. In fact, levels of Dscam have been found critical to neuronal function in Drosophila affecting nerve growth, synaptic targeting and neuronal physiology ( Cvetkovska et al, 2013 ; Lowe et al, 2018 ; Hernández et al, 2023 ). Moreover, Dscam has also been identified as a target of Fragile X messenger ribonucleoprotein 1 (Fmr1) that together with mRNA modification pathways impacts on local translation important for neuronal functions such as learning and memory ( Cvetkovska et al, 2013 ; Haussmann et al, 2022 ; Anreiter et al, 2023 ).…”

Memory consolidation in honey bees is enhanced by down-regulation ofDown Syndrome Cell Adhesion Moleculeand changes its alternative splicing

“…Our finding that Dscam splicing changes upon learning further supports that the Dscam splicing pattern is not fixed and can change on demand. In fact, levels of Dscam have been found critical to neuronal function in Drosophila affecting nerve growth, synaptic targeting and neuronal physiology (Cvetkovska et al, 2013, Lowe et al, 2018, Hernández et al, 2023). Moreover, Dscam has also been identified as a target of Fragile X messenger ribonucleoprotein 1 (Fmr1) that together with mRNA modification pathways impacts on local translation important for neuronal functions such as learning and memory (Cvetkovska et al, 2013, Haussmann, 2022, Anreiter et al, 2023).…”

Getting connected: Pathfinding and synaptogenesis in neural development, evolution, and disease

“…In contrast, vertebrates have just two DSCAM molecules. Despite this, Hern andez et al 10 make the remarkable observation that DSCAM may similarly regulate innervation of the gut in Drosophila and humans. Trisomy for DSCAM in Down syndrome patients is associated with Hirschsprung syndrome and a lack of enteric neurons in the colon.…”