神经元形成细胞类型特定的形态,这些形态由细胞表面分子及其控制树突生长的细胞事件形成。一个生长规则是树突自我回避,通过避免同胞分支,树突在神经元的领土内均匀分布。在哺乳动物神经元中,树突的自我回避是由一大家族的细胞识别分子,称为成簇的原钙粘蛋白(cPcdhs)调节的。遗传和分子研究表明,cPcdhs介导自树突之间的嗜性识别和排斥。然而,该模型尚未通过对开发过程中的自我回避的直接调查进行测试。这里,我们对树突形态发生进行了实时成像和四维(4D)量化,以定义动力学和cPcdh依赖的自我回避机制。我们专注于小鼠视网膜星爆无长突细胞(SAC),这需要γ-Pcdhs(Pcdhgs)和自我/非自我识别来建立刻板的放射状形态,同时允许树突状与相邻的SAC相互作用。通过形态发生,SAC延伸树突状突起,反复填充生长的乔木,并与附近的自枝状突起接触并缩回。与非自接触突起相比,自我接触的事件有更长的寿命,和一个子集持续为循环。在没有Pcdhgs的情况下,非自接触动力学不受影响,但自接触缩回显着减少。自接触桥梁积累,导致树突状过程的捆绑和乔木形状的破坏。通过实时跟踪枝晶自回避,我们的发现表明,γ-Pcdhs介导了接触同胞树突之间的自我识别和退缩。我们的结果还说明了自我回避如何塑造随机和空间填充的树突状生长,以在哺乳动物神经元中形成稳健的模式。
Neurons form cell-type-specific morphologies that are shaped by cell-surface molecules and their cellular events governing
dendrite growth. One growth rule is
dendrite self-avoidance, whereby dendrites distribute uniformly within a neuron\'s territory by avoiding sibling branches. In mammalian neurons,
dendrite self-avoidance is regulated by a large family of cell-recognition molecules called the clustered protocadherins (cPcdhs). Genetic and molecular studies suggest that the cPcdhs mediate homophilic recognition and repulsion between self-dendrites. However, this model has not been tested through direct investigation of self-avoidance during development. Here, we performed live imaging and four-dimensional (4D) quantifications of
dendrite morphogenesis to define the dynamics and cPcdh-dependent mechanisms of self-avoidance. We focused on the mouse retinal starburst amacrine cell (SAC), which requires the gamma-Pcdhs (Pcdhgs) and self/non-self-recognition to establish a stereotypic radial morphology while permitting dendritic interactions with neighboring SACs. Through morphogenesis, SACs extend dendritic protrusions that iteratively fill the growing arbor and contact and retract from nearby self-dendrites. Compared to non-self-contacting protrusions, self-contacting events have longer lifetimes, and a subset persists as loops. In the absence of the Pcdhgs, non-self-contacting dynamics are unaffected but self-contacting retractions are significantly diminished. Self-contacting bridges accumulate, leading to the bundling of dendritic processes and disruption to the arbor shape. By tracking
dendrite self-avoidance in real time, our findings establish that the γ-Pcdhs mediate self-recognition and retraction between contacting sibling dendrites. Our results also illustrate how self-avoidance shapes stochastic and space-filling dendritic outgrowth for robust pattern formation in mammalian neurons.