Kim Namsuk, Min Kwang Wook, Kang Kyung Hwa, Lee Eun Jung, Kim Hyoung-Tai, Moon Kyunghwan, Choi Jiheon, Le Dai, Lee Sang-Hee, Kim Jin Woo
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
KAIST Institute of BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Elife. 2014 Sep 8;3:e02671. doi: 10.7554/eLife.02671.
Retinal ganglion cell (RGC) axons of binocular animals cross the midline at the optic chiasm (OC) to grow toward their synaptic targets in the contralateral brain. Ventral anterior homeobox 1 (Vax1) plays an essential role in the development of the OC by regulating RGC axon growth in a non-cell autonomous manner. In this study, we identify an unexpected function of Vax1 that is secreted from ventral hypothalamic cells and diffuses to RGC axons, where it promotes axonal growth independent of its transcription factor activity. We demonstrate that Vax1 binds to extracellular sugar groups of the heparan sulfate proteoglycans (HSPGs) located in RGC axons. Both Vax1 binding to HSPGs and subsequent penetration into the axoplasm, where Vax1 activates local protein synthesis, are required for RGC axonal growth. Together, our findings demonstrate that Vax1 possesses a novel RGC axon growth factor activity that is critical for the development of the mammalian binocular visual system.
双眼视觉动物的视网膜神经节细胞（RGC）轴突在视交叉（OC）处穿过中线，向对侧脑内的突触靶点生长。腹侧前部同源框1（Vax1）通过非细胞自主方式调节RGC轴突生长，在视交叉的发育中起重要作用。在本研究中，我们发现Vax1具有意想不到的功能，它由下丘脑腹侧细胞分泌并扩散到RGC轴突，在那里它促进轴突生长，且与它的转录因子活性无关。我们证明Vax1与位于RGC轴突的硫酸乙酰肝素蛋白聚糖（HSPG）的细胞外糖基团结合。Vax1与HSPG的结合以及随后穿透到轴质（Vax1在轴质中激活局部蛋白质合成）对于RGC轴突生长都是必需的。总之，我们的研究结果表明Vax1具有一种新型的RGC轴突生长因子活性，这对于哺乳动物双眼视觉系统的发育至关重要。
