Ectodysplasin-A signaling is a key integrator in the lacrimal gland - cornea feedback loop

• Published in: Development (Cambridge) Vol. 146; no. 14
• Main Authors: Kuony, Alison, Ikkala, Kaisa, Kalha, Solja, Magalhães, Ana Cathia, Pirttiniemi, Anniina, Michon, Frederic
• Format: Journal Article
• Language: English
• Published: England 01-07-2019
• Subjects: Tear film; Ectodysplasin; Cornea; Lacrimal gland; Wound healing
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.176693

The lack of Ectodysplasin (Eda) signaling leads to dry eye symptoms, which were so far only associated to altered Meibomian glands. Here, we used loss-of-function (
) mutant mice to unravel the impact of Eda signaling on lacrimal gland formation, maturation and subsequent physiological function. Our study demonstrates that
activity is dispensible during lacrimal gland embryonic development. However, by using a transcriptomic approach, we show that Eda pathway is necessary for proper cell terminal differentiation in lacrimal gland epithelium and correlated with a modified expression of secreted factors commonly found in the tear film. Finally, we discovered that lacrimal glands present a bilateral reduction of Eda signaling activity in response to unilateral corneal injury. This observation hints towards a role for Eda pathway in controlling the switch from basal to reflex tears, to support corneal wound healing. Collectively, our data suggest a crucial implication of Eda signaling in the cornea - lacrimal gland feedback loop, both in physiological and pathophysiological conditions. Our findings demonstrate that Eda downstream targets could help alieviate dry eye symptoms for XLHED patients.