Department of Biological Sciences and KAIST Stem Cell Center, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
Neurovascular Unit, Korea Brain Research Institute, Daegu, 41062, Republic of Korea.
Exp Mol Med. 2023 Feb;55(2):385-400. doi: 10.1038/s12276-023-00930-4. Epub 2023 Feb 3.
In binocular animals that exhibit stereoscopic visual responses, the axons of retinal ganglion cells (RGCs) connect to brain areas bilaterally by forming a commissure called the optic chiasm (OC). Ventral anterior homeobox 1 (Vax1) contributes to the formation of the OC, acting endogenously in optic pathway cells and exogenously in growing RGC axons. Here, we generated Vax1 mice expressing the Vax1 mutant, which is incapable of intercellular transfer. We found that RGC axons cannot take up Vax1 protein from the Vax1 mouse optic stalk (OS) and grow slowly to arrive at the hypothalamus at a late stage. The RGC axons of Vax1 mice connect exclusively to ipsilateral brain areas after failing to access the midline, resulting in reduced visual acuity and abnormal oculomotor responses. Overall, our study provides physiological evidence for the necessity of intercellular transfer of Vax1 and the importance of the bilateral RGC axon projection in proper visuomotor responses.
在表现出立体视觉反应的双目动物中,视网膜神经节细胞 (RGC) 的轴突通过形成称为视交叉 (OC) 的交叉连接到大脑的双侧区域。腹侧同源框 1 (Vax1) 有助于 OC 的形成,在视神经通路细胞中发挥内源性作用,在生长中的 RGC 轴突中发挥外源性作用。在这里,我们生成了表达不能进行细胞间转移的 Vax1 突变体的 Vax1 小鼠。我们发现,RGC 轴突不能从 Vax1 小鼠的视柄 (OS) 摄取 Vax1 蛋白,并且生长缓慢,晚期才能到达下丘脑。Vax1 小鼠的 RGC 轴突在无法到达中线后仅与同侧的大脑区域连接,导致视力下降和异常眼球运动反应。总体而言,我们的研究为 Vax1 的细胞间转移的必要性以及双侧 RGC 轴突投射在适当的视觉运动反应中的重要性提供了生理学证据。