Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Dev Cell. 2019 Jan 28;48(2):229-244.e4. doi: 10.1016/j.devcel.2018.12.015. Epub 2019 Jan 17.
The mechanisms that pattern and maintain dendritic arbors are key to understanding the principles that govern nervous system assembly. The activity of presynaptic axons has long been known to shape dendrites, but activity-independent functions of axons in this process have remained elusive. Here, we show that in Caenorhabditis elegans, the axons of the ALA neuron control guidance and extension of the 1° dendrites of PVD somatosensory neurons independently of ALA activity. PVD 1° dendrites mimic ALA axon guidance defects in loss-of-function mutants for the extracellular matrix molecule MIG-6/Papilin or the UNC-6/Netrin pathway, suggesting that axon-dendrite adhesion is important for dendrite formation. We found that the SAX-7/L1CAM cell adhesion molecule engages in distinct molecular mechanisms to mediate extensions of PVD 1° dendrites and maintain the ALA-PVD axon-dendritic fascicle, respectively. Thus, axons can serve as critical scaffolds to pattern and maintain dendrites through contact-dependent but activity-independent mechanisms.
塑造和维持树突分支的机制是理解神经系统组装原则的关键。突触前轴突的活动长期以来一直被认为可以塑造树突，但轴突在这个过程中的非活动依赖性功能仍然难以捉摸。在这里，我们表明，在秀丽隐杆线虫中，ALA 神经元的轴突可以独立于 ALA 活性控制 PVD 感觉神经元的 1°树突的导向和延伸。PVD 1°树突在细胞外基质分子 MIG-6/Papilin 或 UNC-6/Netrin 通路的功能丧失突变体中模拟了 ALA 轴突导向缺陷，这表明轴突-树突黏附对于树突形成很重要。我们发现，SAX-7/L1CAM 细胞黏附分子分别通过不同的分子机制来介导 PVD 1°树突的延伸和维持 ALA-PVD 轴突-树突束。因此，轴突可以通过依赖接触但非活动依赖性的机制作为塑造和维持树突的关键支架。
