Gomis-Rüth Susana, Wierenga Corette J, Bradke Frank
Axonal Growth and Regeneration, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany.
Curr Biol. 2008 Jul 8;18(13):992-1000. doi: 10.1016/j.cub.2008.06.026.
Developing neurons can change axonal and dendritic fate upon axonal lesion, but it is unclear whether neurons retain such plasticity when they are synaptically interconnected. 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 microm) led to the transformation of a dendrite into an axon (identity change), whereas distal cuts (>35 microm) induced axon regrowth, similar to what is seen in young neurons. 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. 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.
发育中的神经元在轴突损伤后可改变轴突和树突命运，但尚不清楚当神经元通过突触相互连接时是否仍保留这种可塑性。为了探究成熟神经元的极性是否可逆，我们切断了解离培养和器官型培养中绿色荧光蛋白标记的海马神经元的轴突，发现一个新的轴突从成熟的树突长出。再生反应与剩余残端的长度相关：近端轴突切断术（<35微米）导致树突转变为轴突（身份改变），而远端切断（>35微米）诱导轴突再生，类似于在年轻神经元中观察到的情况。在寻找可能决定轴突身份的远端轴突中的假定标志物时，我们将重点放在微管的稳定性上，微管在早期发育过程中调节神经元的初始极化。我们发现功能极化的神经元在远端轴突中含有比例特别高的稳定微管。此外，微管的药物稳定化足以诱导从分化的树突中形成多个轴突。我们的数据表明，整合到功能网络中的成熟神经元在极性方面仍然具有灵活性，并且在初始轴突选择过程中起作用的机制可以被重新激活，以诱导轴突从功能成熟的树突中生长出来。
