Elsevier

Developmental Biology

Volume 491, November 2022, Pages 1-12
Developmental Biology

Multiple roles of Pax6 in postnatal cornea development

https://doi.org/10.1016/j.ydbio.2022.08.006Get rights and content
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Highlights

  • Transcription factor Pax6 is required for postnatal corneal development.

  • Pax6-deficient ocular surface ectoderm develops exclusively into conjunctiva.

  • Conjunctivalisation of the cornea leads to the loss of the limbal region.

  • Pax6-deficient corneal epithelial cells are defective in intercellular adhesion.

  • Loss of intercellular adhesion is accompanied by differentiation defects.

Abstract

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.

Keywords

Eye
Development
Cornea
Pax6
Conditional knockout
E-cadherin
Keratins

Data availability

No data was used for the research described in the article.

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