Institute of Surgical Pathology, University Hospital Zurich, CH-8091 Zurich, Switzerland.
J Neurosci. 2011 Apr 6;31(14):5262-70. doi: 10.1523/JNEUROSCI.4897-10.2011.
Peanut agglutinin-binding disaccharides and chondroitin sulfate mark transient mesenchymal barriers to advancing motor and sensory axons innervating the hindlimbs during chick development. Here we show that the vast majority of these carbohydrates are at the critical stage and location attached to the versican splice variants V0 and V1. We reveal that the isolated isoforms of this extracellular matrix proteoglycan suppress axon extension at low concentrations and induce growth cone collapse and rapid retraction at higher levels. Moreover, we demonstrate that versican V0 and/or V1, recombinantly expressed in collagen-I gels or ectopically deposited in the hindlimbs of chicken embryos in ovo, cause untimely defasciculation and axon stalling. Consequently, severe disturbances of nerve patterning are observed in the versican-treated embryos. Our experiments emphasize the inhibitory capacity of versicans V0 and V1 in axonal growth and evidence for their function as basic guidance cues during development of the peripheral nervous system.
花生凝集素结合的二糖和硫酸软骨素标记发育中鸡的后肢运动和感觉轴突的短暂间充质屏障。在这里，我们表明，这些碳水化合物的绝大多数都附着在弹性蛋白聚糖的剪接变体 V0 和 V1 上，处于关键阶段和位置。我们揭示了这种细胞外基质蛋白聚糖的分离异构体在低浓度下抑制轴突延伸，并在较高水平诱导生长锥塌陷和快速回缩。此外，我们证明，在胶原蛋白凝胶中重组表达的弹性蛋白聚糖 V0 和/或 V1 或异位沉积在鸡胚后肢中，会导致过早的去纤维和轴突停滞。因此，在弹性蛋白聚糖处理的胚胎中观察到神经模式形成的严重干扰。我们的实验强调了 V0 和 V1 在轴突生长中的抑制能力，并证明了它们在周围神经系统发育过程中作为基本导向线索的功能。
