O'Dell Ryan S, Cameron David A, Zipfel Warren R, Olson Eric C
Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York 13210, and.
Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853.
J Neurosci. 2015 Jul 29;35(30):10659-74. doi: 10.1523/JNEUROSCI.1629-15.2015.
The mechanisms controlling cortical dendrite initiation and targeting are poorly understood. Multiphoton imaging of developing mouse cortex reveals that apical dendrites emerge by direct transformation of the neuron's leading process during the terminal phase of neuronal migration. During this ∼110 min period, the dendritic arbor increases ∼2.5-fold in size and migration arrest occurs below the first stable branch point in the developing arbor. This dendritic outgrowth is triggered at the time of leading process contact with the marginal zone (MZ) and occurs primarily by neurite extension into the extracellular matrix of the MZ. In reeler cortices that lack the secreted glycoprotein Reelin, a subset of neurons completed migration but then retracted and reorganized their arbor in a tangential direction away from the MZ soon after migration arrest. For these reeler neurons, the tangential oriented primary neurites were longer lived than the radially oriented primary neurites, whereas the opposite was true of wild-type (WT) neurons. Application of Reelin protein to reeler cortices destabilized tangential neurites while stabilizing radial neurites and stimulating dendritic growth in the MZ. Therefore, Reelin functions as part of a polarity signaling system that links dendritogenesis in the MZ with cellular positioning and cortical lamination.
Whether the apical dendrite emerges by transformation of the leading process of the migrating neuron or emerges de novo after migration is completed is unclear. Similarly, it is not clear whether the secreted glycoprotein Reelin controls migration and dendritic growth as related or separate processes. Here, multiphoton microscopy reveals the direct transformation of the leading process into the apical dendrite. This transformation is coupled to the successful completion of migration and neuronal soma arrest occurs below the first stable branch point of the nascent dendrite. Deficiency in Reelin causes the forming dendrite to avoid its normal target area and branch aberrantly, leading to improper cellular positioning. Therefore, this study links Reelin-dependent dendritogenesis with migration arrest and cortical lamination.
控制皮质树突起始和靶向的机制目前了解甚少。对发育中的小鼠皮质进行多光子成像显示，在神经元迁移的末期，顶端树突通过神经元领先进程的直接转变而出现。在这约110分钟的时间段内，树突分支大小增加约2.5倍，并且在发育中的分支的第一个稳定分支点下方发生迁移停滞。这种树突生长在领先进程与边缘区（MZ）接触时被触发，并且主要通过神经突延伸到MZ的细胞外基质中而发生。在缺乏分泌型糖蛋白Reelin的reeler皮质中，一部分神经元完成迁移，但在迁移停滞后不久，它们就缩回并沿切线方向远离MZ重新组织其分支。对于这些reeler神经元，切线方向的初级神经突比径向方向的初级神经突寿命更长，而野生型（WT）神经元则相反。将Reelin蛋白应用于reeler皮质会使切线神经突不稳定，同时稳定径向神经突并刺激MZ中的树突生长。因此，Reelin作为极性信号系统的一部分发挥作用，该系统将MZ中的树突发生与细胞定位和皮质分层联系起来。
顶端树突是通过迁移神经元的领先进程转变而出现，还是在迁移完成后重新出现尚不清楚。同样，也不清楚分泌型糖蛋白Reelin是作为相关过程还是独立过程来控制迁移和树突生长。在这里，多光子显微镜揭示了领先进程直接转变为顶端树突。这种转变与迁移的成功完成相关联，并且神经元胞体在新生树突的第一个稳定分支点下方发生停滞。Reelin缺乏会导致正在形成的树突避开其正常目标区域并异常分支，从而导致细胞定位不当。因此，本研究将依赖Reelin的树突发生与迁移停滞和皮质分层联系起来。
