Dscam1

 

Dscam1

Pathogen recognition is essential for an effective and specific immune response. Species can evolve diversity of immune recognition and effector molecules, e.g., through alternative splicing. Dscam1 (Down syndrome cell adhesion molecule 1) is a fascinating and complex gene with dual functions in insect and crustacean pathogen defence and neuronal guidance. The complexity of the Dscam1 gene lies within its extreme variability, which is mediated by mutually exclusive alternative splicing that can create tens of thousands of different isoforms. Much attention has recently been placed on this gene because it has been proposed to respond specifically to different pathogens, and although previous work has found evidence for an involvement in immunity, its role is far from fully understood (for reviews see Armitage, Peuß & Kurtz 2015; Armitage & Brites 2016; Armitage et al 2017).

We have used diverse approaches to understand more about specific immune responses and Dscam1: first in collaboration with Ignacio Bravo (CNRS, Montpellier) we examined the evolutionary history of the Dscam gene family and the alternatively spliced exons to attempt to understand when the massive amount of diversity that this gene encodes evolved (Armitage et al. 2012). Second, in collaboration with Dietmar Schmucker (VIB Leuven, Belgium) and Wei Chen (Max Delbrück Centre for Molecular Medicine, Berlin, Germany) we used RNA deep sequencing to test whether different Dscam1 exon variants are transcribed in response to bacterial infection in whole flies and in an insect cell line (Armitage et al. 2014). Unexpectedly we found no support for this idea using our experimental conditions. We then addressed whether Dscam1 plays a role in fitness-related traits in D. melanogaster and a second insect model, Tribolium castaneum. Once again, our results contrasted with our predictions in that they did not support an essential immune-related role for Dscam1: pathogen exposure via septic and oral exposure did not result in changes in mRNA expression, and Dscam1 RNAi knockdown in T. castaneum whole body followed by bacteria exposure did not negatively affect survival (Peuß et al. 2016). However, our results showed that RNAi mediated Dscam1 knockdown had a tremendous negative impact on reproduction and behaviour of T. castaneum, thus opening the research avenue of fitness related traits for this intriguing gene. We still have a lot to understand about how Dscam1 functions in the immune system of insects and crustaceans – this is the topic of a review, whereby questions were presented to six researchers on the current status of Dscam1 research into immunity and what their ideas are for future perspectives (Armitage et al. 2017).