Abstract
MicroRNA-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.
Highlights
During development, neurons are assembled into functional neural pathways through a series of tightly regulated steps involving neurogenesis, neural fate specification, the extension of axons and dendrites, the morphogenesis of axons and dendrites to initiate synaptogenesis, and the culling out of excessive and inappropriate synapses[1]
Because the adult-onset elevation of miR-34 expression plays an essential role in inhibiting chronic neural deterioration in the aged brain[7], we investigated whether miR-34 functions in the inhibition of axotomy-induced axon degeneration in olfactory sensory neurons (OSNs) or developmentally related γaxon pruning in mushroom body (MB) neurons
We investigated the role of Drosophila miR-34 in γaxon pruning in MB neurons to identify pathways that contribute to axon remodeling in developing MB neurons
Summary
Neurons are assembled into functional neural pathways through a series of tightly regulated steps involving neurogenesis, neural fate specification, the extension of axons and dendrites, the morphogenesis of axons and dendrites to initiate synaptogenesis, and the culling out of excessive and inappropriate synapses[1]. In Drosophila, two other types of large-scale neurite degeneration, including injury-induced axon degeneration in olfactory sensory neurons (OSNs) and developmentally related large-scale axon pruning in mushroom body (MB) γneurons, have been investigated extensively for their underlying molecular mechanisms[8,9]. The transforming growth factor (TGF)- βreceptor, Baboon (Babo), and its downstream target molecule, Smad on X (Smox), influence axon pruning of MB γneurons by regulating the expression of the EcR isoform, EcR-B120 It remains unclear whether miRNAs are involved in these two types of axon degenerative processes. Our findings regarding how miRNAs regulate developmentally related large-scale axon degeneration in Drosophila provide new insight into the regulatory mechanisms involved in nervous system development
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