Abstract
SummaryAxon pruning is critical for sculpting precise neural circuits. Although axon pruning has been described in the literature for decades, relatively little is known about the molecular and cellular mechanisms that govern axon pruning in vivo. Here, we show that the epigenetic reader Kismet (Kis) is required for developmental axon pruning in Drosophila mushroom bodies. Kis binds to cis-regulatory elements of the steroid hormone receptor ecdysone receptor (ecr) gene and is necessary for activating expression of EcR-B1. Kis promotes the active H3K36 di- and tri-methylation and H4K16 acetylation histone marks at the ecr locus. We show that transgenic EcR-B1 can rescue axon pruning and memory defects associated with loss of Kis and that the histone deacetylase inhibitor SAHA also rescues these phenotypes. EcR protein abundance is the cell-autonomous, rate-limiting step required to initiate axon pruning in Drosophila, and our data suggest this step is under the epigenetic control of Kis.
Highlights
The elimination and refinement of synaptic connections is an integral part of normal development in vertebrates and invertebrates alike
Kismet Is Required for mushroom bodies (MBs) Pruning We have previously shown that Kismet protein is widely expressed throughout the larval brain, including in the MB neurons (Melicharek et al, 2010)
To characterize the pruning defects previously observed in kis mutant MB neurons, we utilized the mosaic analysis with a repressible cell marker (MARCM) system to generate homozygous mutant neuroblast clones tagged with a membrane-bound GFP (UAS:mCD8GFP) using the 201y-Gal4 driver (Lee and Luo, 1999; Melicharek et al, 2010; Schuldiner et al, 2008; Yang et al, 1995)
Summary
The elimination and refinement of synaptic connections is an integral part of normal development in vertebrates and invertebrates alike. Inappropriate synapses need to be eliminated to establish functional organization of the neuronal circuitry (Tau and Peterson, 2010). The pruning of these exuberant connections can occur on a small scale, as with dendritic remodeling, or on a large scale, such as with axon retraction and degeneration, with each type occurring through distinct molecular mechanisms (Low and Cheng, 2006). Precise control of axon pruning is critical for proper nervous system function, as defects in pruning have been well documented to lead to developmental neurological and psychiatric disorders (Tau and Peterson, 2010).
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