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The spinocerebellar ataxia 8 noncoding RNA causes neurodegeneration and associates with staufen in Drosophila. Curr. Biol. 14, 302–308. 18. Marchut, A.J., and Hall, C.K. (2006). Side-chain interactions determine amyloid formation by model polyglutamine peptides in molecular dynamics simulations. Biophys. J. 90, 4574–4584. Developmental Biology Institute of Marseille, CNRS UMR 6216, Universite ´ de la Me ´ diterrane ´ e, Campus de Luminy, Case 907, 13288 Marseille Cedex 9, France. E-mail: birman@ibdml.univ-mrs.fr DOI: 10.1016/j.cub.2008.06.023 Neuronal Polarization: Old Cells Can Learn New Tricks Regeneration was once thought to be exclusive to young neurons. Now, a new study shows that functional and interconnected hippocampal neurons have the potential to quickly recover from losing an axon. They do so by signaling a dendrite to change its specification and replace the missing axon by rearranging the microtubule cytoskeleton. Eric S. Sweet 1,2 and Bonnie L. Firestein 1, * Neurons are highly polarized cells, with neurotransmitters from neighboring axons binding to receptors on dendrites, thus allowing for directional signaling. Disruption of this polarization by severing the axon eliminates the ability of a neuron to function. In young, immature neurons, restoration of polarity can occur by transforming a dendrite into a new axon [1]. An important, clinically relevant, question is whether this can also occur in older, mature neurons. In a new study reported in a recent issue of Current Biology, Gomis-Ru ¨ th et al. [2] show that it is possible for neurons that have already grown to maturity and established functional connections to regenerate their axons. This ability seems to stem from the neuron’s capacity to continually remodel its microtubule cytoskeleton, despite the highly ordered structure needed to maintain neuronal connections. The ability for the microtubules to be remodeled has been suggested before but has not yet been shown in mature neurons [3]. The cytoskeletal structure of neurons differs in axons and dendrites in several ways. Axons contain the microtubule-associated protein (MAP) tau while dendrites contain MAP2. The microtubules are also oriented differently in axons and dendrites, with microtubules being mostly unidirectional in the axon and bi-directional in the dendrite. In addition, axons contain more stable microtubules than do dendrites. Young, migrating neurons go through phases in which they are multipolar and eventually settle into a unipolar state before finishing their migration [4]. This process of polarization would have to involve the distinction of the axon from the many nascent extensions resulting in orientation and stability changes in the microtubule cytoskeleton. It was previously unknown if these changes were permanent. In this new study, Gomis-Ru ¨ th et al. [2] show that mature neurons with established connections form new axons when the original axon is cut and that microtubule stability plays an important role in this process. Significantly, the authors show that new axon formation occurs both in vitro and ex vivo [2]. The authors found that axotomy closer to the cell body results in the transformation of a dendrite into a new axon. The identity of the new axons was confirmed by a number of features, including the formation of functional synapses [2]. Distal axotomy caused regrowth of the original axon (Figure 1). These results raise the question of how transformation of a dendrite into an axon occurs. It was recently shown that microtubule stabilization helps specify initial neuronal polarization [5]. To understand whether microtubule stability plays a role in axonal determination in mature neurons, Gomis-Ru ¨ th et al. [2] stabilized the microtubules of neurons in culture with taxol. Surprisingly, they found that this treatment causes formation of multiple axons. The study demonstrates for the first time that microtubule stability is sufficient to cause a mature neuron to form multiple axons. The transformation and growth of dendrites into axons continues after taxol has been washed out, suggesting that the initial stabilization of microtubules may be the critical signal for axonal growth. Dispatch R661 brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by Elsevier - Publisher Connector