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

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 ␣-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.

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly

“…Of these, only lens fiber cells destroy nuclei within the cell. Despite many investigations over the past century, the molecular mechanism(s) by which fiber cell denucleation occurs has remained a mystery (Vrensen et al, 1991(Vrensen et al, , 2004He et al, 1998He et al, , 2010Ivanov et al, 2005;Xie et al, 2007;Rivera et al, 2009;Wang et al, 2010;Gupta et al, 2011;Ma et al, 2011;Jarrin et al, 2012;Rodrigues et al, 2013). Preliminary work suggested that the lens 'appropriates' normal mitotic mechanisms in order to accomplish denucleation: specifically, that nuclear membrane disassembly occurs after phosphorylation of nuclear lamins and that stabilization of the CDK1 inhibitor p27 KIP1 delays denucleation (Caceres et al, 2010).…”

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

“…Single nucleotide polymorphism (SNP) linkage analysis mapped the causal mutation to proximal chromosome 16, between 29 Mb and 50 Mb (Table S1). Loss-of-function mutations in two genes, Gsk3b and Dlg1, inside this chromosomal region have been associated with cleft palate in mice (He et al, 2010;Rivera et al, 2009), but targeted sequencing of all exons and exon-intron boundaries of these two genes did not find any mutation in the ENU1483 line.…”

The Scribble–Dlg–Lgl Module in Cell Polarity Regulation

“…More recent work has revealed direct roles for mouse Dlg homologues in cell polarity and developmental processes. In contrast to other family members, Dlg1 (SAP97) mutant mice are neonatal lethal, displaying craniofacial defects and kidney, urogenital, and lens development defects (Caruana and Bernstein 2001;Naim et al 2005;Mahoney et al 2006;Iizuka-Kogo et al 2007;Rivera et al 2009). More recently, Dlg1 null mice were shown to also display defects in skeletogenesis of the trunk and limb structures and, importantly, similarly to loss of Scribble, defects in neural tube, eyelid closure, and in the disorganization of the stereociliary bundles in the cochlea (Rivera et al 2013).…”