Characterization of Axon Innervation to the Extraocular Muscles in Wild Type Mice

Certain forms of human strabismus result from abnormal ocular cranial nerve development, such that the nerves do not reach appropriate eye muscle targets. This causes stereotyped defects in eye movement. Various human eye movement disorders are now being modeled in mice to further understand their etiology. However, little is known about the three-dimensional innervation pattern of ocular cranial nerves onto extraocular muscles during mouse development. The intention of this research project is to gain an understanding of the normal developmental growth and innervation of ocular cranial nerves III, IV, and VI from their brainstem nuclei to the extraocular muscles in wild type mice to form a database from which to compare innervation patterns of normal and mutant mouse models. ISL^MN:GFP reporter mice on a mixed background were used to visualize ocular cranial nerve input onto immunostained extraocular muscles during embryonic development.  Histological sections were reconstructed into 3D images at multiple embryonic time points between E11.5 and E17.5 to determine innervation patterns. Characterization of normal extraocular muscle innervation during mouse development will facilitate the identification of innervation defects in mouse models of human eye movement disorders. This, in turn, should provide insights into strabismus pathogenesis that will eventually be beneficial to those who suffer from these disorders.