Multiple roles of Pax6 in postnatal cornea development

0568318 - ÚMG 2023 RIV US eng J - Journal Article
Sunny, Sweetu Susan - Láchová, Jitka - Dupačová, Naoko - Kozmik, Zbyněk
Multiple roles of Pax6 in postnatal cornea development.
Developmental Biology. Roč. 491, Nov (2022), s. 1-12. ISSN 0012-1606. E-ISSN 1095-564X
R&D Projects: GA MŠMT(CZ) LM2018126; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) ED1.1.00/02.0109; GA ČR GA21-27364S
Institutional support: RVO:68378050
Keywords : eye * development * cornea * pax6 * conditional knockout * E-cadherin * Keratins
OECD category: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology
Impact factor: 2.7, year: 2022
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/abs/pii/S0012160622001580?via%3Dihub

Mammalian corneal development is a multistep process, including formation of the corneal epithelium (CE), endothelium and stroma during embryogenesis, followed by postnatal stratification of the epithelial layers and continuous renewal of the epithelium to replace the outermost corneal cells. Here, we employed the Cre-loxP system to conditionally deplete Pax6 proteins in two domains of ocular cells, i.e., the ocular surface epithelium (cornea, limbus and conjunctiva) (OSE) or postnatal CE via K14-cre or Aldh3-cre, respectively. Earlier and broader inactivation of Pax6 in the OSE resulted in thickened OSE with CE and limbal cells adopting the conjunctival keratin expression pattern. More restricted depletion of Pax6 in postnatal CE resulted in an abnormal cornea marked by reduced epithelial thickness despite increased epithelial cell proliferation. Immunofluorescence studies revealed loss of intermediate filament Cytokeratin 12 and diffused expression of adherens junction components, together with reduced tight junction protein, Zonula occludens-1. Furthermore, the expression of Cytokeratin 14, a basal cell marker in apical layers, indicates impaired differentiation of CE cells. Collectively, our data demonstrate that Pax6 is essential for maintaining proper differentiation and strong intercellular adhesion in postnatal CE cells, whereas limbal Pax6 is required to prevent the outgrowth of conjunctival cells to the cornea.
Permanent Link: https://hdl.handle.net/11104/0339654