Oculomotor Nerve Development: Slit/Robo Regulates Midline Crossing

Abstract

The oculomotor nerve has a significant role in innervating the extraocular muscles of the eye that are necessary for the proper positioning and movement of the eye. Defects in the development of the oculomotor system can result in strabismus, a misalignment of the eyes, which left uncorrected can lead to partial blindness. Surprisingly, little is known about the embryonic development of the oculomotor nerve. Oculomotor neurons (OMNs) innervating the dorsal rectus undergo a unique migration through the midline to achieve a contralateral innervation pattern. Slit/Robo signaling has been shown to have an important role in the guidance of midline crossing axons, but less is known about midline crossing neurons. Here, we characterize normal migration of oculomotor neurons and analyze the oculomotor phenotypes of Slit1/2 double mutants and Robo 1/2 double mutants. We find that Slit/Robo repulsion (Slit2 predominant) is important for the maintenance of the ipsilateral position of OMNs seen in early development. In addition, Robo2 seems to be the main receptor governing this restriction. Therefore, the modulation of Slit/Robo signaling serves as an important mechanism governing the migration of dorsal rectus innervating OMNs.