Ocular motor nerve development in the presence and absence of extraocular muscle

Suzanne M. Michalak, Mary C. Whitman, Jong G. Park, Max Tischfield, Elaine H. Nguyen, Elizabeth C. Engle

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

PURPOSE. To spatially and temporally define ocular motor nerve development in the presence and absence of extraocular muscles (EOMs). METHODS. Myf5cre mice, which in the homozygous state lack EOMs, were crossed to an IslMN:GFP reporter line to fluorescently label motor neuron cell bodies and axons. Embryonic day (E) 11.5 to E15.5 wild-type and Myf5cre/cre:IslMN:GFP whole mount embryos and dissected orbits were imaged by confocal microscopy to visualize the developing oculomotor, trochlear, and abducens nerves in the presence and absence of EOMs. E11.5 and E18.5 brainstems were serially sectioned and stained for Islet1 to determine the fate of ocular motor neurons. RESULTS. At E11.5, all three ocular motor nerves in mutant embryos approached the orbit with a trajectory similar to that of wild-type. Subsequently, while wild-type nerves send terminal branches that contact target EOMs in a stereotypical pattern, the Myf5cre/creocular motor nerves failed to form terminal branches, regressed, and by E18.5 two-thirds of their corresponding motor neurons died. Comparisons between mutant and wild-type embryos revealed novel aspects of trochlear and oculomotor nerve development. CONCLUSIONS. We delineated mouse ocular motor nerve spatial and temporal development in unprecedented detail. Moreover, we found 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.

Original languageEnglish (US)
Pages (from-to)2388-2396
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume58
Issue number4
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Fingerprint

Oculomotor Muscles
Motor Neurons
Orbit
Trochlear Nerve
Oculomotor Nerve
Axons
Embryonic Structures
Brain Stem
Cues
Abducens Nerve
Mesoderm
Confocal Microscopy

All Science Journal Classification (ASJC) codes

  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Ophthalmology

Cite this

Michalak, Suzanne M. ; Whitman, Mary C. ; Park, Jong G. ; Tischfield, Max ; Nguyen, Elaine H. ; Engle, Elizabeth C. / Ocular motor nerve development in the presence and absence of extraocular muscle. In: Investigative Ophthalmology and Visual Science. 2017 ; Vol. 58, No. 4. pp. 2388-2396.
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abstract = "PURPOSE. To spatially and temporally define ocular motor nerve development in the presence and absence of extraocular muscles (EOMs). METHODS. Myf5cre mice, which in the homozygous state lack EOMs, were crossed to an IslMN:GFP reporter line to fluorescently label motor neuron cell bodies and axons. Embryonic day (E) 11.5 to E15.5 wild-type and Myf5cre/cre:IslMN:GFP whole mount embryos and dissected orbits were imaged by confocal microscopy to visualize the developing oculomotor, trochlear, and abducens nerves in the presence and absence of EOMs. E11.5 and E18.5 brainstems were serially sectioned and stained for Islet1 to determine the fate of ocular motor neurons. RESULTS. At E11.5, all three ocular motor nerves in mutant embryos approached the orbit with a trajectory similar to that of wild-type. Subsequently, while wild-type nerves send terminal branches that contact target EOMs in a stereotypical pattern, the Myf5cre/creocular motor nerves failed to form terminal branches, regressed, and by E18.5 two-thirds of their corresponding motor neurons died. Comparisons between mutant and wild-type embryos revealed novel aspects of trochlear and oculomotor nerve development. CONCLUSIONS. We delineated mouse ocular motor nerve spatial and temporal development in unprecedented detail. Moreover, we found 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.",
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Ocular motor nerve development in the presence and absence of extraocular muscle. / Michalak, Suzanne M.; Whitman, Mary C.; Park, Jong G.; Tischfield, Max; Nguyen, Elaine H.; Engle, Elizabeth C.

In: Investigative Ophthalmology and Visual Science, Vol. 58, No. 4, 01.04.2017, p. 2388-2396.

Research output: Contribution to journalArticle

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T1 - Ocular motor nerve development in the presence and absence of extraocular muscle

AU - Michalak, Suzanne M.

AU - Whitman, Mary C.

AU - Park, Jong G.

AU - Tischfield, Max

AU - Nguyen, Elaine H.

AU - Engle, Elizabeth C.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - PURPOSE. To spatially and temporally define ocular motor nerve development in the presence and absence of extraocular muscles (EOMs). METHODS. Myf5cre mice, which in the homozygous state lack EOMs, were crossed to an IslMN:GFP reporter line to fluorescently label motor neuron cell bodies and axons. Embryonic day (E) 11.5 to E15.5 wild-type and Myf5cre/cre:IslMN:GFP whole mount embryos and dissected orbits were imaged by confocal microscopy to visualize the developing oculomotor, trochlear, and abducens nerves in the presence and absence of EOMs. E11.5 and E18.5 brainstems were serially sectioned and stained for Islet1 to determine the fate of ocular motor neurons. RESULTS. At E11.5, all three ocular motor nerves in mutant embryos approached the orbit with a trajectory similar to that of wild-type. Subsequently, while wild-type nerves send terminal branches that contact target EOMs in a stereotypical pattern, the Myf5cre/creocular motor nerves failed to form terminal branches, regressed, and by E18.5 two-thirds of their corresponding motor neurons died. Comparisons between mutant and wild-type embryos revealed novel aspects of trochlear and oculomotor nerve development. CONCLUSIONS. We delineated mouse ocular motor nerve spatial and temporal development in unprecedented detail. Moreover, we found 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.

AB - PURPOSE. To spatially and temporally define ocular motor nerve development in the presence and absence of extraocular muscles (EOMs). METHODS. Myf5cre mice, which in the homozygous state lack EOMs, were crossed to an IslMN:GFP reporter line to fluorescently label motor neuron cell bodies and axons. Embryonic day (E) 11.5 to E15.5 wild-type and Myf5cre/cre:IslMN:GFP whole mount embryos and dissected orbits were imaged by confocal microscopy to visualize the developing oculomotor, trochlear, and abducens nerves in the presence and absence of EOMs. E11.5 and E18.5 brainstems were serially sectioned and stained for Islet1 to determine the fate of ocular motor neurons. RESULTS. At E11.5, all three ocular motor nerves in mutant embryos approached the orbit with a trajectory similar to that of wild-type. Subsequently, while wild-type nerves send terminal branches that contact target EOMs in a stereotypical pattern, the Myf5cre/creocular motor nerves failed to form terminal branches, regressed, and by E18.5 two-thirds of their corresponding motor neurons died. Comparisons between mutant and wild-type embryos revealed novel aspects of trochlear and oculomotor nerve development. CONCLUSIONS. We delineated mouse ocular motor nerve spatial and temporal development in unprecedented detail. Moreover, we found 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.

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