September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Canonical Jagged-1-Notch1 signaling axis is required for meibocyte differentiation during Meibomian gland morphogenesis
Author Affiliations & Notes
  • Chia-Yang Liu
    School of Optometry, Indiana University, Bloomington, Indiana, United States
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States
  • Yujin Zhang
    School of Optometry, Indiana University, Bloomington, Indiana, United States
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States
  • Simi Goins
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States
  • Mindy Kay Call
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States
  • Winston W Y Kao
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States
  • Footnotes
    Commercial Relationships   Chia-Yang Liu, None; Yujin Zhang, None; Simi Goins, None; Mindy Call, None; Winston Kao, None
  • Footnotes
    Support  NIH/RO1 EY-21501, EY-23086, EY-011845, EY-021768, unrestricted Departmental grant of Research to Prevent Blindness and Ohio Eye Research Foundation
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5660. doi:
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      Chia-Yang Liu, Yujin Zhang, Simi Goins, Mindy Kay Call, Winston W Y Kao; Canonical Jagged-1-Notch1 signaling axis is required for meibocyte differentiation during Meibomian gland morphogenesis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5660.

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

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Abstract

Purpose : To demonstrate that Jagged1/Notch1→N1-ICD/Rbp-jk/MAML1→Klf4/5 axis is critical for meibocyte differentiation during Meibomian gland morphogenesis.

Methods : Compound transgenic mice consisting of K14-rtTA/tetO-Cre and floxed Jagged1, Dll1, Notch1, Notch2, Rbp-jk, and Rosa26-dnMAML1 alleles, respectively, were used to ablate the gene of interest in a spatial-temporal specific manner from embryonic (E) day 14, before meibocyte cell differentiation. Phenotypic analyses of the resultant ocular surface were compared to the wild-type littermates at various stages. Oil red O (ORO) staining and antibodies specific against elongation of very long chain fatty acids protein 4 (ELOL4) were performed to identify lipid synthesis. Antibodies against the Krüppel-like family of transcription factor (KLF)-4 and -5 were performed to identify meibocyte differentiation.

Results : Ablation of Dll1 or Noth2 from K14-positive cells did not reveal any phenotypical abnormality. However, loss of Jagged1, Notch1, Rbp-jk expression, and gain of dnMAML1 expression in K14-positive cells all manifested severe ocular surface malformation including corneal ulceration and conjunctivitis sicca. Immunohistological analysis revealed that both lipid synthesis and expression of ELOVL4, Klf-4 and -5 were diminished.

Conclusions : Our data indicate that ligand Jagged-1 but not Dll1 and receptor Notch1 but not Notch2 are adopted to execute Notch juxtacrine signaling in ocular surface epithelia, which is of paramount importance for meibocyte differentiation in Meibomian gland morphogenesis during development.

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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