Drosophila microRNA-34 Impairs Axon Pruning of Mushroom Body γ Neurons by Downregulating the Expression of Ecdysone Receptor

• DOI: 10.1038/srep39141
• Publication Date: 2016-12-24T21:26:56Z
• Authors: Yen-Wei Lai; Sao-Yu Chu; Jia-Yi Wei; Chu-Ya Cheng; Jian-Chiuan Li; Po-Lin Chen; Chun-Hong Chen; Hung-Hsiang Yu
• Keywords: 0301 basic medicine; Receptors, Steroid; Neuronal Plasticity; Down-Regulation; Gene Expression Regulation, Developmental; Axotomy; Cell Differentiation; Article; Olfactory Receptor Neurons; MicroRNAs; 03 medical and health sciences; Drosophila melanogaster; Animals; Mushroom Bodies

AbstractMicroRNA-34 (miR-34) is crucial for preventing chronic large-scale neurite degeneration in the aged brain of Drosophila melanogaster. Here we investigated the role of miR-34 in two other types of large-scale axon degeneration in Drosophila: axotomy-induced axon degeneration in olfactory sensory neurons (OSNs) and developmentally related axon pruning in mushroom body (MB) neurons. Ectopically overexpressed miR-34 did not inhibit axon degeneration in OSNs following axotomy, whereas ectopically overexpressed miR-34 in differentiated MB neurons impaired γ axon pruning. Intriguingly, the miR-34-induced γ axon pruning defect resulted from downregulating the expression of ecdysone receptor B1 (EcR-B1) in differentiated MB γ neurons. Notably, the separate overexpression of EcR-B1 or a transforming growth factor- β receptor Baboon, whose activation can upregulate the EcR-B1 expression, in MB neurons rescued the miR-34-induced γ axon pruning phenotype. Future investigations of miR-34 targets that regulate the expression of EcR-B1 in MB γ neurons are warranted to elucidate pathways that regulate axon pruning, and to provide insight into mechanisms that control large-scale axon degeneration in the nervous system.