September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Normal development of the oculomotor system in mice
Author Affiliations & Notes
  • Suzanne Michalak
    Neurology, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, United States
    University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States
  • Mary Whitman
    Ophthalmology, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, United States
  • Alicia Nugent
    Neurology, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, United States
  • Jong Park
    Neurology, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, United States
    Duke University School of Medicine, Boston, Massachusetts, United States
  • Long Cheng
    Neurology, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, United States
  • Elizabeth Engle
    Neurology, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, United States
    Howard Hughes Medical Institute, Chevy Chase, Maryland, United States
  • Footnotes
    Commercial Relationships   Suzanne Michalak, None; Mary Whitman, None; Alicia Nugent, None; Jong Park, None; Long Cheng, None; Elizabeth Engle, None
  • Footnotes
    Support  Howard Hughes Medical Institute Medical Research Fellows Program, Knights Templar Pediatric Eye Foundation Career Starter Award, Children's Hospital Ophthalmology Foundation, HHMI, Harvard-Vision Clinical Scientist Development Program 5K12EY016335
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4570. doi:
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    • Get Citation

      Suzanne Michalak, Mary Whitman, Alicia Nugent, Jong Park, Long Cheng, Elizabeth Engle; Normal development of the oculomotor system in mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4570.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Disorders in development of the human ocular motor system can have debilitating consequences, including complex strabismus and amblyopia. Although mice are often used as models for congenital diseases of the oculomotor system, there have been few studies to date detailing the normal development of the murine ocular motor system. In this report, we systematically detail the embryonic development of the oculomotor system in mice and highlight optimal methods for imaging and studying the system at critical time points during development.

Methods : Mice at developmental ages ranging from embryonic day 9.5 (E9.5) to birth were imaged using a combination of confocal imaging of whole mounts, sections, or dissected orbits. Islet-GFP and HB9-GFP reporter lines were used to label the developing oculomotor, trochlear, and abducens nuclei and axons. Developing muscles were labeled with antibody staining of alpha smooth muscle actin or Pitx-2, or with Myf5-cre mice crossed to a TdTomato reporter line. For each embryonic day, five or more embryos were analyzed.

Results : The development of the ocular motor system follows a stereotypic, highly conserved sequence. The neurons in the oculomotor nucleus form at E9.5-E10.5 and begin sending out projections as early as E10. Around the same time, a primordial anlage that will eventually become the extraocular muscles can be identified posterior to the developing eye. The oculomotor nerve reaches the developing eye musculature by E11. It later branches at 2 stereotypic locations: one where the superior and inferior divisions separate, and a second where the inferior division separates to innervate individual muscles. The abducens nerve reaches the orbit approximately 6-12 hours after the oculomotor nerve and contacts the developing muscle anlage by E11.5. The trochlear nerve reaches the orbit between E12-12.5. At E12.5, individual extraocular muscles can first be distinguished. Neuromuscular synapses can first be identified at E17.5.

Conclusions : Understanding the normal time course of development is critical to the study of congenital disorders of the oculomotor system, and this report is the first of its kind to methodically detail the developmental time course of the oculomotor system in mice and present refined methods for studying this system.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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