September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
PITX2, FOXC1 and CYP1B1 mediate ocular fissure closure via interactions between the neural crest and optic cup
Author Affiliations & Notes
  • Antionette L. Williams
    University of Michigan Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Brenda L Bohnsack
    University of Michigan Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Footnotes
    Commercial Relationships   Antionette L. Williams, None; Brenda Bohnsack, None
  • Footnotes
    Support  Edward Mallincrodt Jr. Foundation; Research to Prevent Blindness
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 230. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Antionette L. Williams, Brenda L Bohnsack; PITX2, FOXC1 and CYP1B1 mediate ocular fissure closure via interactions between the neural crest and optic cup. Invest. Ophthalmol. Vis. Sci. 2016;57(12):230.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Anterior segment dysgenesis, as observed in Axenfeld-Rieger syndrome, Peters Anomaly and congenital glaucoma, exists in conjunction with colobomata, suggesting that neural crest development and ocular fissure closure are interconnected processes. In these studies, we used zebrafish to investigate the role of genes associated with anterior segment dysgenesis (pitx2, foxc1, and cyp1b1) in regulating interactions between the neural crest and optic cup.

Methods : Zebrafish eye and neural crest development was analyzed using morpholino oligonucleotides (MO) or mRNA injections. Live imaging of transgenic embryos, in situ hybridization, methacrylate sectioning and microscopy were used to assess migration and gene expression.

Results : Pitx2a and foxc1a were initially expressed in the neural crest-derived periocular mesenchyme along the ventral eye border in the area of the ocular fissure. Foxc1a was also subsequently expressed in neural crest-derived smooth muscle cells in the hyaloid vasculature. Knockdown of Pitx2a or Foxc1a resulted in the increased expression of cyp1b1 in the retinal pigment epithelium and retina of the ocular fissure. Further, the decreased expression of Pitx2a (B,B’) or Foxc1 (C,C’) caused colobomata. Similarly, the overexpression of zebrafish or human cyp1b1 (D,D’) inhibited inferior ocular fissure closure, resulting in prominent colobomata. Cyp1b1 negatively regulated retinal pax6a and pax6b expression. Consistently, knockdown of Pax6a or Pax6b resulted in coloboma formation, which was partially rescued through concurrent Cyp1b1 knockdown.

Conclusions : Pitx2a and Foxc1a subpopulations of neural crest regulate ocular fissure closure via Cyp1b1 and Pax6 in the retina and retinal pigment epithelium. These studies provide insight into the roles of Pitx2, Foxc1 and Cyp1b1 in eye development and the relationship between the ocular fissure and neural crest in the pathogenesis of congenital eye diseases.

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

 

At 72-96 hours post fertilization Tg(sox10::EGFP) embryos showed that Pitx2a (B,B’) or Foxd3 (C,C’) MO knockdown resulted in colobomata (arrowheads) and malformed jaw (arrows) and pharyngeal arches compared with controls (A,A’). Similarly, cyp1b1 overexpression (D,D’) caused colobomata and disrupted neural crest jaw and pharyngeal arch formation.

At 72-96 hours post fertilization Tg(sox10::EGFP) embryos showed that Pitx2a (B,B’) or Foxd3 (C,C’) MO knockdown resulted in colobomata (arrowheads) and malformed jaw (arrows) and pharyngeal arches compared with controls (A,A’). Similarly, cyp1b1 overexpression (D,D’) caused colobomata and disrupted neural crest jaw and pharyngeal arch formation.

×
×

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.

×