Cell-autonomous requirements for Dlg-1 for lens epithelial cell structure and fiber cell morphogenesis

Dev Dyn. 2009 Sep;238(9):2292-308. doi: 10.1002/dvdy.22036.

Abstract

Cell polarity and adhesion are thought to be key determinants in organismal development. In Drosophila, discs large (dlg) has emerged as an important regulator of epithelial cell proliferation, adhesion, and polarity. Herein, we investigated the role of the mouse homolog of dlg (Dlg-1) in the development of the mouse ocular lens. Tissue-specific ablation of Dlg-1 throughout the lens early in lens development led to an expansion and disorganization of the epithelium that correlated with changes in the distribution of adhesion and polarity factors. In the fiber cells, differentiation defects were observed. These included alterations in cell structure and the disposition of cell adhesion/cytoskeletal factors, delay in denucleation, and reduced levels of alpha-catenin, pERK1/2, and MIP26. These fiber cell defects were recapitulated when Dlg-1 was disrupted only in fiber cells. These results suggest that Dlg-1 acts in a cell autonomous manner to regulate epithelial cell structure and fiber cell differentiation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aquaporins / metabolism
  • Blotting, Western
  • Cell Differentiation* / genetics
  • Cell Differentiation* / physiology
  • Cell Polarity / genetics
  • Cell Polarity / physiology
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism*
  • Eye Proteins / metabolism
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental
  • Lens, Crystalline / cytology*
  • Lens, Crystalline / embryology
  • Lens, Crystalline / metabolism*
  • Male
  • Mice
  • Mice, Mutant Strains
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • SAP90-PSD95 Associated Proteins
  • alpha Catenin / metabolism

Substances

  • Aquaporins
  • Eye Proteins
  • Nerve Tissue Proteins
  • SAP90-PSD95 Associated Proteins
  • alpha Catenin
  • aquaporin 0
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3

Grant support