Clements Reena, Wright Kevin M
Neuroscience Graduate Program, Oregon Health&Science University, Portland, OR 97239, USA.
Neuroscience Graduate Program, Oregon Health&Science University, Portland, OR 97239, USA; Vollum Institute, Oregon Health&Science University, Portland, OR 97239, USA.
Dev Biol. 2018 Oct 15;442(2):210-219. doi: 10.1016/j.ydbio.2018.08.010. Epub 2018 Aug 24.
In the developing visual system, retinal ganglion cell (RGC) axons project from the retina to several distal retinorecipient regions in the brain. Several molecules have been implicated in guiding RGC axons in vivo, but the role of extracellular matrix molecules in this process remains poorly understood. Dystroglycan is a laminin-binding transmembrane protein important for formation and maintenance of the extracellular matrix and basement membranes and has previously been implicated in axon guidance in the developing spinal cord. Using two genetic models of functional dystroglycan loss, we show that dystroglycan is necessary for correct sorting of contralateral and ipsilateral RGC axons at the optic chiasm. Mis-sorted axons still target retinorecipient brain regions and persist in adult mice, even after axon pruning is complete. Our results highlight the importance of the extracellular matrix for axon sorting at an intermediate choice point in the developing visual circuit.
在发育中的视觉系统中,视网膜神经节细胞(RGC)轴突从视网膜投射到大脑中的几个远端视网膜接受区域。已有几种分子被认为在体内引导RGC轴突,但细胞外基质分子在此过程中的作用仍知之甚少。肌营养不良聚糖是一种与层粘连蛋白结合的跨膜蛋白,对细胞外基质和基底膜的形成和维持很重要,此前已被认为与发育中的脊髓轴突导向有关。使用两种功能性肌营养不良聚糖缺失的遗传模型,我们表明肌营养不良聚糖对于视交叉处对侧和同侧RGC轴突的正确分选是必需的。分选错误的轴突仍然靶向视网膜接受脑区,并在成年小鼠中持续存在,即使轴突修剪完成后也是如此。我们的结果强调了细胞外基质在发育中的视觉回路中间选择点进行轴突分选的重要性。