Résumé
The Amyloid Precursor Protein (APP) is linked to Alzheimer’s disease. Appl is the single Drosophila APP ortholog and is expressed in all neurons throughout development. Appl was previously shown to modulate, cell-autonomously, axon outgrowth in the mushroom bodies (MBs), the fly olfactory memory center. Furthermore, Appl knockdown in the MBs results in loss of memory following the association of odorants with electric shocks. Nevertheless, the memory defects of flies devoid of Appl remains unknown because Appl d flies, carrying the only known null allele, show an abnormal response to electric shock. We found that Appl d affects the normal function of vnd , the gene just proximal to Appl . We report here that vnd is required for MB β-branch axon outgrowth. Moreover, vnd is expressed in neurons close to, but not within, the MB during development and is required non-cell-autonomously for MB axon outgrowth. To decipher developmental and memory defects specifically due to a loss of only Appl function, we generated a precise Appl null allele ( Appl C2 . 1 ) by CRISPR/Cas9 genomic engineering. With Appl C2 . 1 , we confirmed the partial requirement for Appl in MB axon outgrowth but found no defects of electric shock avoidance, allowing us to test for potential memory defects. Appl C2 . 1 flies showed a complete loss of long-term memory which was fully rescued by MB-restricted expression of Appl + only during the adult stage. Therefore, we demonstrate that the complete lack of Appl affects memory independently from structural developmental defects.