Visuomotor anomalies in achiasmatic mice expressing a transfer-defective Vax1 mutant

Abstract

Vision: bringing the two sides togetherA protein regulating gene expression called Vax1 is essential for building the optic chiasm (OC), a brain structure where nerves from the left and right eyes cross to the other side of the brain. Signals from both eyes must be integrated for space and depth perception. Although some cues guiding optic nerve growth are known, those for the OC are not. Jin Woo Kim at the Korea Advanced Institute of Science and Technology, Daejeon, South Korea, and co-workers investigated visual development in mice expressing a mutant Vax1. They found that the mutant Vax1 could not support the optic nerve, which grew slowly and failed to connect to the other side of the brain. Consequently, the mice had impaired depth perception and low vision. These results show the importance of Vax1 for the development of binocular vision. 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(AA/AA) mice expressing the Vax1(AA) mutant, which is incapable of intercellular transfer. We found that RGC axons cannot take up Vax1(AA) protein from the Vax1(AA/AA) mouse optic stalk (OS) and grow slowly to arrive at the hypothalamus at a late stage. The RGC axons of Vax1(AA/AA) 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.