Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway

Laura Grisanti, Ekaterina Revenkova, Ronald E. Gordon, Carlo Iomini

Research output: Contribution to journalArticle

Abstract

Primary cilia have been linked to signaling pathways involved in cell proliferation, cell motility and cell polarity. Defects in ciliary function result in developmental abnormalities and multiple ciliopathies. Patients affected by severe ciliopathies, such as Meckel syndrome, present several ocular surface disease conditions of unclear pathogenesis. Here, we show that primary cilia are predominantly present on basal cells of the mouse corneal epithelium (CE) throughout development and in the adult. Conditional ablation of cilia in the CE leads to an increase in proliferation and vertical migration of basal corneal epithelial cells (CECs). A consequent increase in cell density of suprabasal layers results in a thicker than normal CE. Surprisingly, in cilia-deficient CE, cilia-mediated signaling pathways, including Hh and Wnt pathways, were not affected but the intensity of Notch signaling was severely diminished. Although Notch1 and Notch2 receptors were expressed normally, nuclear Notch1 intracellular domain (N1ICD) expression was severely reduced. Postnatal development analysis revealed that in ciliadeficient CECs downregulation of the Notch pathway precedes cell proliferation defects. Thus, we have uncovered a function of the primary cilium in maintaining homeostasis of the CE by balancing proliferation and vertical migration of basal CECs through modulation of Notch signaling.

Original languageEnglish (US)
Pages (from-to)2160-2171
Number of pages12
JournalDevelopment (Cambridge)
Volume143
Issue number12
DOIs
StatePublished - Jun 15 2016
Externally publishedYes

Fingerprint

Cilia
Corneal Epithelium
Homeostasis
Epithelial Cells
Notch2 Receptor
Notch1 Receptor
Cell Proliferation
Multiple Abnormalities
Cell Polarity
Wnt Signaling Pathway
Eye Diseases
Cell Movement
Down-Regulation
Cell Count

Keywords

  • Cornea
  • Epithelium
  • Mouse
  • Notch signaling
  • Ocular surface
  • Primary cilia
  • Wound healing

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway. / Grisanti, Laura; Revenkova, Ekaterina; Gordon, Ronald E.; Iomini, Carlo.

In: Development (Cambridge), Vol. 143, No. 12, 15.06.2016, p. 2160-2171.

Research output: Contribution to journalArticle

Grisanti, Laura ; Revenkova, Ekaterina ; Gordon, Ronald E. ; Iomini, Carlo. / Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway. In: Development (Cambridge). 2016 ; Vol. 143, No. 12. pp. 2160-2171.
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