JAM-C Is Important for Lens Epithelial Cell Proliferation and Lens Fiber Maturation in Murine Lens Development

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  • 作者:Qihang Sun, Jiani Li, Jingyu Ma, Yuxing Zheng, Rong Ju, Xuri Li, Xiangrong Ren, Lijuan Huang, Rongyuan Chen, Xuhua Tan, Lixia Luo
  • 期刊:INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
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Purpose:The underlying mechanism of congenital cataracts caused by deficiency or mutation of junctional adhesion molecule C (JAM-C) gene remains unclear. Our study aims to elucidate the abnormal developmental process inJamc?/?lenses and reveal the genes related to lens development that JAM-C may regulate.Methods:Jamcknockout (Jamc?/?) mouse embryos and pups were generated for in vivo studies. Four key developmental stages from embryonic day (E) 12.5 to postnatal day (P) 0.5 were selected for the following experiments. Hematoxylin and eosin staining was used for histological analysis. The 5-bromo-2′-deoxyuridine (BrdU) incorporation assay and TUNEL staining were performed to label lens epithelial cell (LEC) proliferation and apoptosis, respectively. Immunofluorescence and Western blot were used to analyze the markers of lens epithelium, cell cycle exit, and lens fiber differentiation.Results:JAM-C was expressed throughout the process of lens development. Deletion ofJamcresulted in decreased lens size and disorganized lens fibers, which arose from E16.5 and aggravated gradually. The LECs ofJamc?/?lenses showed decreased quantity and proliferation, accompanied with reduction of key transcription factor, FOXE3. The fibers inJamc?/?lenses were disorganized. Moreover,Jamc-deficient lens fibers showed significantly altered distribution patterns of Cx46 and Cx50. The marker of fiber homeostasis, γ-crystallin, was also decreased in the inner cortex and core fibers ofJamc?/?lenses.Conclusions:Deletion of JAM-C exhibits malfunction of LEC proliferation and fiber maturation during murine lens development, which may be related to the downregulation of FOXE3 expression and abnormal localization patterns of Cx46 and Cx50.

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