School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia.
Mech Dev. 2012 Jul;129(5-8):109-24. doi: 10.1016/j.mod.2012.05.004. Epub 2012 May 17.
The anterior commissure forms the first axon connections between the two sides of the embryonic telencephalon. We investigated the role of the transmembrane receptor Frizzled-3a in the development of this commissure using zebrafish as an experimental model. Knock down of Frizzled-3a resulted in complete loss of the anterior commissure. This defect was accompanied by a loss of the glial bridge, expansion of the slit2 expression domain and perturbation of the midline telencephalic-diencephalic boundary. Blocking Slit2 activity following knock down of Frizzled-3a effectively rescued the anterior commissure defect which suggested that Frizzled-3a was indirectly controlling the growth of axons across the rostral midline. We have shown here that Frizzled-3a is essential for normal development of the commissural plate and that loss-of-function causes Slit2-dependent defects in axon midline crossing in the embryonic vertebrate forebrain. These data supports a model whereby Wnt signaling through Frizzled-3a attenuates expression of Slit2 in the rostral midline of the forebrain. The absence of Slit2 facilitates the formation of a midline bridge of glial cells which is used as a substrate for commissural axons. In the absence of this platform of glia, commissural axons fail to cross the rostral midline of the forebrain.
前连合是胚胎端脑两侧之间的第一个轴突连接。我们使用斑马鱼作为实验模型，研究了跨膜受体卷曲蛋白 3a 在这种连合发育中的作用。卷曲蛋白 3a 的敲低导致前连合完全缺失。这种缺陷伴随着神经胶质桥的丢失、 slit2 表达域的扩张以及中线端脑-间脑边界的扰动。在卷曲蛋白 3a 敲低后阻断 Slit2 的活性，有效地挽救了前连合缺陷，这表明卷曲蛋白 3a 是间接控制轴突穿过颅中线的生长。我们在这里表明，卷曲蛋白 3a 对于连合板的正常发育是必不可少的，并且功能丧失导致 Slit2 依赖性的轴突中线穿越在胚胎脊椎动物前脑中的缺陷。这些数据支持了一种模型，即卷曲蛋白 3a 通过 Wnt 信号传导减弱了前脑中线中 Slit2 的表达。Slit2 的缺失促进了神经胶质细胞中线桥的形成，该桥被用作连合轴突的基质。在没有这种神经胶质平台的情况下，连合轴突无法穿过前脑的颅中线。
