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Suzanne Marie Michalak, Jong Park, Mary Whitman, Max Tischfield, Elizabeth Engle; Ocular motor nerve development in the presence and absence of extraocular muscle. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2999.
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© ARVO (1962-2015); The Authors (2016-present)
Spatially and temporally define ocular motor nerve development in the presence and absence of extraocular muscles (EOMs).
Myf5cre mice, which in the homozygous state lack EOMs, were crossed to an Isl:GFP reporter line to fluorescently label motor neuron cell bodies and axons. Embryonic day (E) 11.5 to E15.5 wildtype and Myf5cre/cre whole mount embryos or dissected orbits were imaged by confocal microscopy to visualize the developing oculomotor, trochlear, and abducens nerves in the presence and absence of EOMs. E18.5 brainstems were serially sectioned and stained for Islet1 to determine the fate of ocular motor neurons.
At E11.5, all three ocular motor nerves in mutant embryos approach the orbit with a trajectory identical to that of wildtype. Subsequently, while wildtype nerves send terminal branches that contact target EOMs, the Myf5cre/cre ocular motor nerves fail to form terminal branches, regress, and their corresponding motor neurons die. Comparisons between mutant and wildtype embryos reveal unique aspects of trochlear and oculomotor nerve development.
We have delineated ocular motor nerve spatial and temporal development in unprecedented detail. We find that EOMs are not necessary for initial outgrowth and guidance of ocular motor axons from the brainstem to the orbit but are required for their terminal branching and survival. These data suggest that intermediate targets in the mesenchyme provide cues necessary for appropriate targeting of ocular motor axons to the orbit, while EOM cues are responsible for terminal branching and motor neuron survival.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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