Journal
DEVELOPMENTAL BIOLOGY
Volume 334, Issue 1, Pages 243-252Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2009.07.028
Keywords
Cited2; Corneal epithelial cell; K12 expression; Wound healing
Categories
Funding
- National Institute of Health [R01HL075436, HL75427]
- NHMRC Senior Research Fellow
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Cited2 is an important transcriptional cofactor involved in multiple organ development. Gene pro. le analysis has identified Cited2 as one of the transcription factors expressed at high levels in adult mouse cornea. To address the function of Cited2 in corneal morphogenesis, we deleted Cited2 in surface ectoderm derived ocular structures including cornea by crossing Cited2-floxed mice with Le-Cre transgenic mice. Cited2(flox/flox); Le-Cre(+) eyes invariably displayed corneal opacity and developed spontaneous corneal neovascularization at older age. Fewer layers of corneal epithelial cells and the absence of cytokeratin 12 (K12) expression featured Cited2 deficient postnatal and adult eyes. Cited2 deficient cornea exhibited impaired healing in response to corneal epithelial debridement by manifesting abnormal histology, lack of K12 expression and corneal neovascularization. Moreover, mechanistic studies suggest that Cited2 may play a role in corneal morphogenesis in part through modulating the expression of Pax6 and Klf4. Collectively, these findings demonstrate a novel function of Cited2 in postnatal corneal morphogenesis and maintenance. Our study will help better understand the molecular mechanisms involved in corneal biology, and more importantly, it may provide a valuable animal model for testing therapeutics in the treatment of corneal disorders, especially blindness as a result of corneal epithelial cell deficiency. (C) 2009 Elsevier Inc. All rights reserved.
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