Nerve Regeneration group, Instituto de Biologia Molecular e Celular - IBMC and i3S, Instituto de Inovação e Investigação em Saúde, University of Porto, Porto, Portugal.
Doctoral Program in Molecular and Cell Biology, Instituto de Ciências Biomédicas Abel Salazar-ICBAS, University of Porto, Porto, Portugal.
Dev Neurobiol. 2021 Apr;81(3):300-309. doi: 10.1002/dneu.22747. Epub 2020 Apr 25.
Throughout development, neurons are capable of integrating external and internal signals leading to the morphological changes required for neuronal polarization and axon growth. The first phase of axon elongation occurs during neuronal polarization. At this stage, membrane remodeling and cytoskeleton dynamics are crucial for the growth cone to advance and guide axon elongation. When a target is recognized, the growth cone collapses to form the presynaptic terminal. Once a synapse is established, the growth of the organism results in an increased distance between the neuronal cell bodies and their targets. In this second phase of axon elongation, growth cone-independent molecular mechanisms and cytoskeleton changes must occur to enable axon growth to accompany the increase in body size. While the field has mainly focused on growth-cone mediated axon elongation during development, tension driven axon growth remains largely unexplored. In this review, we will discuss in a critical perspective the current knowledge on the mechanisms guiding axon growth following synaptogenesis, with a particular focus on the putative role played by the axonal cytoskeleton.
在整个发育过程中，神经元能够整合外部和内部信号，导致神经元极化和轴突生长所需的形态变化。轴突伸长的第一阶段发生在神经元极化过程中。在这个阶段，膜重塑和细胞骨架动力学对于生长锥的前进和引导轴突伸长至关重要。当目标被识别时，生长锥塌陷形成突触前末端。一旦建立了突触，生物体的生长就会导致神经元细胞体与其靶标之间的距离增加。在轴突伸长的第二阶段，必须发生生长锥独立的分子机制和细胞骨架变化，以使轴突生长伴随着体型的增加。虽然该领域主要集中在发育过程中生长锥介导的轴突伸长，但张力驱动的轴突生长在很大程度上仍未被探索。在这篇综述中，我们将从批判性的角度讨论指导突触发生后轴突生长的机制的现有知识，特别关注轴突细胞骨架可能发挥的作用。
