Department of Biology/MS 314, University of Nevada, Reno, Nevada, USA.
Dev Dyn. 2023 Jan;252(1):156-171. doi: 10.1002/dvdy.554. Epub 2022 Dec 12.
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).
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.
Our work demonstrates that overexpression of Dscam1 can perturb gut function in a model system.
唐氏综合征（DS）患者患结肠和直肠先天性巨结肠（HSCR）的风险增加 100 倍，这是结肠缺乏肠神经元的一种疾病。DS 的主要候选基因是唐氏综合征细胞黏附分子（DSCAM）的三倍体。
我们发现 Dscam1 蛋白在果蝇肠/口咽神经系统（SNS）中表达。不同的异构体可以平等地拯救轴突 Dscam1 表型。Dscam1 的过表达导致前肠和后肠神经过度生长。显性负性 Dscam1-ΔC 的表达导致前神经截断和后肠神经分支增加。幼虫的运动受到进食状态的影响，我们发现 Dscam1 SNS 表达的幼虫的平均速度降低，而 Dscam1-ΔC 的过表达显著增加了速度。Dscam1 的过表达降低了幼虫肠道清除食物的效率。
我们的工作表明，Dscam1 的过表达可以在模型系统中扰乱肠道功能。
