Deterministic and Stochastic Rules of Branching Govern Dendrite Morphogenesis of Sensory Neurons
Deterministic and Stochastic Rules of Branching Govern Dendrite Morphogenesis of Sensory Neurons
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DOI：
10.1016/j.cub.2020.10.054
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发表时间：
2021-02-08
期刊：
影响因子：
9.2
通讯作者：
Lecuit, Thomas
中科院分区：
文献类型：
--
作者：
Palavalli, Amrutha;Tizon-Escamilla, Nicolas;Lecuit, Thomas
树突形态对于神经元接收的输入的正确整合是必要的。允许神经元获得其类型特异性形态的分支机制仍不清楚。传统上，轴突和树突模式被证明是由分子引导的，提供了确定性线索。然而，基于纯粹统计偏差的确定性和随机机制对树突形状的出现的贡献程度在很大程度上尚不清楚。我们使用果蝇 I 类 vpda 多树突神经元解决这个问题。 vpda 树突形态发生的详细定量分析表明，初级分支在固定方向上非常稳健地生长，尽管次级分支数量和长度显示出随机系统的波动特征。实时跟踪树突和计算模型揭示了神经元形状如何从分支动力学的少数局部统计参数中产生。我们报告了树结构如何反馈分支收缩的局部概率的关键相反方面。子分支促进父分支的稳定，尽管自排斥会促进收缩。最后，我们表明，由粘附分子 Dscam1 介导的自排斥通过在空间上限制垂直于初级分支的稳定生长方向来间接模式化次级分支的生长。因此，次级分支动力学的随机性质和几何反馈的存在强调了自组织在神经元树突形态发生中的重要性。
Dendrite morphology is necessary for the correct integration of inputs that neurons receive. The branching mechanisms allowing neurons to acquire their type-specific morphology remain unclear. Classically, axon and dendrite patterns were shown to be guided by molecules, providing deterministic cues. However, the extent to which deterministic and stochastic mechanisms, based upon purely statistical bias, contribute to the emergence of dendrite shape is largely unknown. We address this issue using the Drosophila class I vpda multi-dendritic neurons. Detailed quantitative analysis of vpda dendrite morphogenesis indicates that the primary branch grows very robustly in a fixed direction, though secondary branch numbers and lengths showed fluctuations characteristic of stochastic systems. Live-tracking dendrites and computational modeling revealed how neuron shape emerges from few local statistical parameters of branch dynamics. We report key opposing aspects of how tree architecture feedbacks on the local probability of branch shrinkage. Child branches promote stabilization of parent branches, although self-repulsion promotes shrinkage. Finally, we show that self-repulsion, mediated by the adhesion molecule Dscam1, indirectly patterns the growth of secondary branches by spatially restricting their direction of stable growth perpendicular to the primary branch. Thus, the stochastic nature of secondary branch dynamics and the existence of geometric feedback emphasize the importance of self-organization in neuronal dendrite morphogenesis.