Regeneration ofDrosophilasensory neuron axons and dendrites is regulated by the Akt pathway involvingPtenand microRNAbantam

Abstract

Both cell-intrinsic and extrinsic pathways govern axon regeneration, but only a limited number of factors have been identified and it is not clear to what extent axon regeneration is evolutionarily conserved. Whether dendrites also regenerate is unknown. Here we report that, like the axons of mammalian sensory neurons, the axons of certain Drosophila dendritic arborization (da) neurons are capable of substantial regeneration in the periphery but not in the CNS, and activating the Akt pathway enhances axon regeneration in the CNS. Moreover, those da neurons capable of axon regeneration also display dendrite regeneration, which is cell type-specific, developmentally regulated, and associated with microtubule polarity reversal. Dendrite regeneration is restrained via inhibition of the Akt pathway in da neurons by the epithelial cell-derived microRNA bantam but is facilitated by cell-autonomous activation of the Akt pathway. Our study begins to reveal mechanisms for dendrite regeneration, which depends on both extrinsic and intrinsic factors, including the PTEN-Akt pathway that is also important for axon regeneration. We thus established an important new model system-the fly da neuron regeneration model that resembles the mammalian injury model-with which to study and gain novel insights into the regeneration machinery.

Cell-intrinsic drivers of dendrite morphogenesis

“…Similarly, the role of organelles such as the primary cilium in dendrite morphogenesis remains to be elucidated. Defects in dendrite morphogenesis have been observed in neurons with conditional deletion of cilia (Song et al, 2012), but the underlying signaling mechanisms remain poorly characterized. The authors suggest that Wnt signaling might be dysregulated, thereby mediating aberrations in dendrite patterning.…”

Centrosomin represses dendrite branching by orienting microtubule nucleation

“…Mature dendrites have a predominantly minus--ends--out microtubule array 18 , nevertheless recent studies identified that anterograde microtubule polymerization events in mature neurons can initiate or extend branches or modulate the size of dendritic spines 19,20 . In addition, the re--initiation of growth and branch formation following injury uses upregulation of microtubule polymerization and polarization in the anterograde direction 21 .…”

Regulation of axon growth by the JIP1-AKT axis

“…Furthermore, the manipulation of the JIP1-AKT axis could represent a potential route for promoting nerve regeneration. There is already evidence that JIP1 promotes regeneration of adult mouse dorsal root ganglion neurons (Barnat et al, 2010) and a number of studies have proposed a role for AKT-mediated signalling in axonal regeneration (Namikawa et al, 2000;Kim et al, 2011;Song et al, 2012).…”