If you have any problems related to the accessibility of any content (or if you want to request that a specific publication be accessible), please contact us at email@example.com.
Development of the Oculomotor Nerve: A Role for Slit Signaling
AuthorBjorke, Brielle M.
AdvisorMastick, Grant S.
Biochemistry and Molecular Biology
AltmetricsView Usage Statistics
The ability to visually locate and follow objects of interest relies on ocular motor systems that control eye movements. The ocular motor system includes motor neurons located in the CNS that innervate the extraocular muscles surrounding the eye. These systems must perform both slow and fast eye muscle movements to accommodate head and body motion, smooth pursuit, vergence and saccadic functions, as well as respond to balance signals from the vestibular-ocular system. Nerves controlling the extraocular muscles (EOM) must function with a high degree of accuracy, thus placing a demand on proper motor neuron development and innervation. Three cranial nerves innervate the EOMs: cranial nerves III, IV and VI. Errors in the development of these nerves can lead to congenital cranial dysinnervation disorders, resulting in eye alignment errors termed strabismus. Among them, Duane syndrome is directly related to errors in the development of the oculomotor nerve, cranial nerve III (nIII). Unfortunately, the fundamental cause of these disorders remains unknown. One way of addressing these problems is to understand development of the oculomotor system at the cellular and molecular level. Although numerous studies have described cellular and molecular events in the development of the hindbrain and spinal motor systems, less attention has been placed on the midbrain. However, the midbrain houses somatic motor neurons that innervate four of the six extraocular muscles, as well as the visceral neurons that innervate the ciliary ganglion to control eye movement and pupil dilation. These populations reside together in the ventral midbrain and are collectively termed neurons of the oculomotor complex (OMC). To begin to understand disorders influencing the function of the oculomotor system I have reviewed known factors influencing the development of the OMC--from initial OMC differentiation to EOM innervation, as well as probed the function of the guidance cue Slit in these processes. This dissertation is divided into four chapters aimed at reviewing events and factors working in OM development (Chapters 1,3) and basic experiments to determine the role that Slit plays in OMC development (Chapters 2,4). In Chapter 1, I review both old and new studies on the development of the midbrain and OMC neurons. Although the development of the OMC has received more recent attention, a complete review is lacking. I begin by describing the components of the vertebrate OMC and the proposed birth date of its somatic and visceral components. I then describe events and factors that regulate OMC development and later cell death. In Chapter 2, I describe the migration of a subset of OMC neurons, the dorsal rectus motor neurons, across the ventral midbrain. To examine factors that may influence this migration, I focused on the expression of classic guidance cues. I further genetically manipulated the expression of these cues to find that the Slit family of midline repellents act to inhibit premature migration. In Chapter 3, I review prior studies of guidance cues and mechanism that guide the outgrowth and navigation of the OMN toward the EOMs.In Chapter 4, I describe preliminary studies to determine the role Slit signals may have in OMN guidance and EOM innervation. The research findings outlined in chapters 2 and 4 add to understanding the cellular and molecular events that lead to proper development of the OMC and cranial nerve III.