Retinal axon guidance at the midline: Chiasmatic misrouting and consequences

The visual representation of the outside world relies on the appropriate connectivity between the eyes and the brain. Retinal ganglion cells are the sole neurons that send an axon from the retina to the brain, and thus the guidance decisions of retinal axons en route to their targets in the brain shape the neural circuitry that forms the basis of vision. Here, we focus on the choice made by retinal axons to cross or avoid the midline at the optic chiasm. This decision allows each brain hemisphere to receive inputs from both eyes corresponding to the same visual hemifield, and is thus crucial for binocular vision. In achiasmatic conditions, all retinal axons from one eye project to the ipsilateral brain hemisphere. In albinism, abnormal guidance of retinal axons at the optic chiasm leads to a change in the ratio of contralateral and ipsilateral projections with the consequence that each brain hemisphere receives inputs primarily from the contralateral eye instead of an almost equal distribution from both eyes in humans. In both cases, this misrouting of retinal axons leads to reduced visual acuity and poor depth perception. While this defect has been known for decades, mouse genetics have led to a better understanding of the molecular mechanisms at play in retinal axon guidance and at the origin of the guidance defect in albinism. In addition, fMRI studies on humans have now confirmed the anatomical and functional consequences of axonal misrouting at the chiasm that were previously only assumed from animal models. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 844-860, 2017.