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Plasticity of Polarization: Changing Dendrites into Axons in Neurons Integrated in Neuronal Circuits

2008; Elsevier BV; Volume: 18; Issue: 13 Linguagem: Inglês

10.1016/j.cub.2008.06.026

1879-0445

Susana Gomis-Rüth, Corette J. Wierenga, Frank Bradke,

Microtubule and mitosis dynamics

Developing neurons can change axonal and dendritic fate upon axonal lesion [1Bradke F. Dotti C.G. Neuronal polarity: vectorial cytoplasmic flow precedes axon formation.Neuron. 1997; 19: 1175-1186Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar, 2Dotti C.G. Banker G.A. Experimentally induced alteration in the polarity of developing neurons.Nature. 1987; 330: 254-256Crossref PubMed Scopus (210) Google Scholar, 3Goslin K. Banker G. Experimental observations on the development of polarity by hippocampal neurons in culture.J. Cell Biol. 1989; 108: 1507-1516Crossref PubMed Scopus (325) Google Scholar, 4Takahashi D. Yu W. Baas P.W. Kawai-Hirai R. Hayashi K. Rearrangement of microtubule polarity orientation during conversion of dendrites to axons in cultured pyramidal neurons.Cell Motil. Cytoskeleton. 2007; 64: 347-359Crossref PubMed Scopus (32) Google Scholar, 5Calderon de Anda F. Gartner A. Tsai L.H. Dotti C.G. Pyramidal neuron polarity axis is defined at the bipolar stage.J. Cell Sci. 2008; 121: 178-185Crossref PubMed Scopus (60) Google Scholar, 6Bradke F. Dotti C.G. Differentiated neurons retain the capacity to generate axons from dendrites.Curr. Biol. 2000; 10: 1467-1470Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar], but it is unclear whether neurons retain such plasticity when they are synaptically interconnected [7Rodriguez J.A. Piddini E. Hasegawa T. Miyagi T. Dotti C.G. Plasma membrane ganglioside sialidase regulates axonal growth and regeneration in hippocampal neurons in culture.J. Neurosci. 2001; 21: 8387-8395Crossref PubMed Google Scholar, 8Arimura N. Kaibuchi K. Neuronal polarity: from extracellular signals to intracellular mechanisms.Nat. Rev. Neurosci. 2007; 8: 194-205Crossref PubMed Scopus (457) Google Scholar]. To address whether polarity is reversible in mature neurons, we cut the axon of GFP-labeled hippocampal neurons in dissociated and organotypic cultures and found that a new axon arose from a mature dendrite. The regenerative response correlated with the length of the remaining stump: proximal axotomies ( 35 μm) induced axon regrowth, similar to what is seen in young neurons [3Goslin K. Banker G. Experimental observations on the development of polarity by hippocampal neurons in culture.J. Cell Biol. 1989; 108: 1507-1516Crossref PubMed Scopus (325) Google Scholar]. Searching for a putative landmark in the distal axon that could determine axon identity, we focused on the stability of microtubules, which regulate initial neuronal polarization during early development [9Witte H. Neukirchen D. Bradke F. Microtubule stabilization specifies initial neuronal polarization.J. Cell Biol. 2008; 180: 619-632Crossref PubMed Scopus (357) Google Scholar]. We found that functionally polarized neurons contain a distinctively high proportion of stable microtubules in the distal axon. Moreover, pharmacological stabilization of microtubules was sufficient to induce the formation of multiple axons out of differentiated dendrites. Our data argue that mature neurons integrated in functional networks remain flexible in their polarity and that mechanisms acting during initial axon selection can be reactivated to induce axon growth out of functionally mature dendrites.