The Drosophila homolog of APP promotes Dscam expression to drive axon terminal growth, revealing interaction between Down syndrome genes

Abstract

Down syndrome (DS) is caused by triplication of human chromosome 21 (HSA21). Although several HSA21 genes have been found to be responsible for aspects of DS, whether and how HSA21 genes interact with each other is poorly understood. DS patients and animal models present with a number of neurological changes, including aberrant connectivity and neuronal morphology. Previous studies have indicated that amyloid precursor protein (APP) and Down syndrome cell adhesion molecule (DSCAM) regulate neuronal morphology and contribute to neuronal aberrations in DS. Here, we report the functional interaction between the Drosophila homologs of these two genes, Amyloid precursor protein-like (Appl) and Dscam (Dscam1). We show that Appl requires Dscam to promote axon terminal growth in sensory neurons. Moreover, Appl increases Dscam protein expression post-transcriptionally. We further demonstrate that regulation of Dscam by Appl does not require the Appl intracellular domain or second extracellular domain. This study presents an example of functional interactions between HSA21 genes, providing insights into the pathogenesis of neuronal aberrations in DS.

Progress and Prospect of Dscam Gene in Drosophila Immunity

“…Since the discovery of the Dscam gene as a highly variable axon guiding receptor on the cell surface of Drosophila melanogaster, our understanding of its function in the nervous system and its evolution in arthropods has been widely expanded. However, we still have a far from complete understanding of the Dscam gene's function in the immune system [3,4]. Therefore, this article mainly reviews the research progress prospects of Dscam genes in fruit fly immunity by understanding the immune mechanism of fruit flies and the immune function of Dscam genes, with the aim of providing a detailed understanding of this gene from another perspective.…”