June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Notch signaling is required for postnatal development of the lacrimal gland
Author Affiliations & Notes
  • Yihua Wu
    Ophthalmology, Columbia University Irving Medical Center, New York, New York, United States
  • Xin Zhang
    Ophthalmology, Columbia University Irving Medical Center, New York, New York, United States
  • Footnotes
    Commercial Relationships   Yihua Wu None; Xin Zhang None
  • Footnotes
    Support  NEI RO1 Grant GG015817
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 180. doi:
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    • Get Citation

      Yihua Wu, Xin Zhang; Notch signaling is required for postnatal development of the lacrimal gland. Invest. Ophthalmol. Vis. Sci. 2023;64(8):180.

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

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Abstract

Purpose : The Notch pathway plays an important role in regulation of cell proliferation and differentiation. A dominant-negative model to downregulate Notch signaling has been reported to cause degeneration of the lacrimal gland, but the specific cellular defects and underlying molecular mechanism have not been examined. We knocked out Notch effector Rbpj to better understand the role of Notch signaling in lacrimal development and the mechanism behind the degeneration.

Methods : Rbpj conditional knockout was generated using Le-Cre, a conditional Cre that is specifically expressed in lacrimal gland epithelial cells at E14 and is fused with an IRES-GFP reporter. Glands were harvested from Rbpj knockouts and wild-type mice from the same litter. Glands were harvested at different stages, between P1 and adult, about a week apart for each stage. Immunohistochemistry was used to stain for protein markers of differentiation and proliferation.

Results : At birth, lacrimal glands with Rbpj conditional knockout did not exhibit any obvious phenotype. At P5, expression of acinar cell differentiation marker Mist1 was drastically reduced, which coincides with collapse of acinar cells. Myoepithelial cells in mutant areas clumped together, but they did not appear to change shape or expression of proteins. Ductal cells in the gland exhibited changes in gene expression but not morphology. The mutant glands progressively degenerate until almost completely gone around P21.

Conclusions : Rbpj is not required during embryonic development of the lacrimal gland, but is required for maturation and maintenance of acini cells after birth.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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