Neuromuscular junction formation in Extraocular muscles of embryonic mice

Abstract

Proper functioning of the visual system depends on correct functioning of the oculomotor system. When the oculomotor system functions correctly, cranial nerves III, IV, and VI migrate to and properly innervate the appropriate extraocular muscles. If proper innervation does not take place, congenital cranial dysinnervation disorders result. One of these disorders is strabismus, a misalignment of the eyes. Despite the importance of the oculomotor system, little is known about the migration and innervation of extraocular muscles embryonically in mice. When a nerve innervates a muscle, a chemical synapse, referred to as a neuromuscular junction (NMJ), is formed. To pinpoint the time of innervation the cranial nerves and NMJs of extraocular muscles were labelled using immunohistochemistry and bungarotoxin between E11.5-E14.5. Extraocular muscles exist as a mass of precursor cells near the eye between E11.5 and E12.5. This precursor mass is innervated by a nerve plexus. By E13.5, the precursor cell mass has segregated and muscles have reached their approximate positions around the eye. By this point each muscle is innervated by its respective cranial nerve. NMJs are visible at E13.5 suggesting they form between E12.5 and 13.5. And at E14 extraocular muscles have reached their final positions around the eye, and NMJs show distinct patterning.