July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Nf2 is required during late stages of optic fissure closure in the developing mouse eye
Author Affiliations & Notes
  • Sabine Fuhrmann
    Ophthal & Vis Sci, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Kelly Spiller
    Ophthal & Vis Sci, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Wesley Sun
    Ophthal & Vis Sci, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Footnotes
    Commercial Relationships   Sabine Fuhrmann, None; Kelly Spiller, None; Wesley Sun, None
  • Footnotes
    Support  Unrestricted Grant to the VEI from RPB, NIH NEI EY24373
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6016. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Sabine Fuhrmann, Kelly Spiller, Wesley Sun; Nf2 is required during late stages of optic fissure closure in the developing mouse eye. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6016.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : During eye morphogenesis, tissue fusion is a critical process. Eye morphogenesis initiates with evagination of the optic vesicles and subsequent formation of the optic cup, which differentiates into retina and retinal pigment epithelium (RPE). Fusion occurs along the ventral side of the optic cup in an area known as the optic fissure (OF; around embryonic day (E) 11.5 in mouse). However, if OF fusion fails, a gap in the ventral eye, coloboma, will persist potentially interfering with vision. Several genes have been identified as instrumental, but the precise mechanisms underlying the fusion events remain poorly understood. Neurofibromin 2 (Nf2; Merlin) is an attractive focus for our study due to its established roles in tumor suppression, apical-basal polarity, and junctional complex formation. It functions to inhibit proliferation through the Hippo signaling pathway by negatively regulating the transcriptional coactivators YAP and TAZ. Our study is aimed to elucidate the role of Nf2 during the complex process of OF closure.

Methods : We generated Nf2 conditional knockout (CKO) embryos by combining constitutive Rx3-Cre with a conditional loss of function allele of Nf2. Nf2 CKO embryos were analyzed at E11.5 and E13.5 using immunohistochemical techniques for cell proliferation, apoptosis, tissue patterning, apicobasal polarity, and cellular junctions.

Results : Nf2 CKO embryos exhibit a coloboma with a narrow gap at E13.5 indicating a role for Nf2 at late stages of OF closure. In the ventral optic cup at E11.5, we did not observe a significant difference in PHH3-labeled cells. In the OF margins, apoptosis and cell polarity appears largely maintained. However, the cell number in the ventral RPE close to the OF is increased in Nf2 CKO mutants and RPE markers can be ectopically upregulated in the OF margins. Currently, we are testing additional ages and markers for Hippo pathway components, cell junctions, proliferation, as well as genetic interaction with Wnt signaling and Mitf.

Conclusions : Our results emphasize a critical role for Nf2 in eye development and, in particular, during OF closure, possibly by regulating RPE patterning and proliferation of neuroepithelial cells lining the OF margins. We hypothesize that Nf2 acts through regulation of the Hippo/YAP-TAZ pathway, consistent with recent studies showing a role for YAP-TAZ in regulating RPE fate in the optic cup.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×