The Drosophila homolog of APP promotes Dscam expression to drive axon terminal growth, revealing interaction between Down syndrome genes.
Sarah PizzanoGabriella R SterneMacy W VelingL Amanda XuTy HergenrederBing YePublished in: Disease models & mechanisms (2023)
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.
Keyphrases
- genome wide
- bioinformatics analysis
- genome wide identification
- copy number
- end stage renal disease
- cerebral ischemia
- cell adhesion
- chronic kidney disease
- ejection fraction
- endothelial cells
- newly diagnosed
- genome wide analysis
- binding protein
- poor prognosis
- spinal cord
- protein protein
- gene expression
- brain injury
- resting state
- subarachnoid hemorrhage
- long non coding rna
- patient reported outcomes
- multiple sclerosis
- pluripotent stem cells