c-myc Regulates Cell Proliferation during Lens Development

Abstract

Myc protooncogenes play important roles in the regulation of cell proliferation, growth, differentiation and survival during development. In various developing organs, c-myc has been shown to control the expression of cell cycle regulators and its misregulated expression is detected in many human tumors. Here, we show that c-myc gene (Myc) is highly expressed in developing mouse lens. Targeted deletion of c-myc gene from head surface ectoderm dramatically impaired ocular organogenesis, resulting in severe microphtalmia, defective anterior segment development, formation of a lens stalk and/or aphakia. In particular, lenses lacking c-myc presented thinner epithelial cell layer and growth impairment that was detectable soon after its inactivation. Defective development of c-myc-null lens was not caused by increased cell death of lens progenitor cells. Instead, c-myc loss reduced cell proliferation, what was associated with an ectopic expression of Prox1 and p27Kip1 proteins within epithelial cells. Interestingly, a sharp decrease in the expression of the forkhead box transcription factor Foxe3 was also observed following c-myc inactivation. These data represent the first description of the physiological roles played by a Myc family member in mouse lens development. Our findings support the conclusion that c-myc regulates the proliferation of lens epithelial cells in vivo and may, directly or indirectly, modulate the expression of classical cell cycle regulators in developing mouse lens.

Xenopus pax6 mutants affect eye development and other organ systems, and have phenotypic similarities to human aniridia patients

“…In other studies, targeted downregulation of the myc gene by morpholino antisense oligonucleotide injection into the blastomeres giving rise to the head region in Xenopus laevis embryos is shown to interfere with eye development (Bellmeyer et al, 2003). A recent study also highlights the role of Myc in cell proliferation during mouse lens development (Cavalheiro et al, 2014). Further studies on the function of myc as a potential mediator of pax6 activity will be an important goal for the future.…”

N-myc regulates growth and fiber cell differentiation in lens development

“…Similar notations were used for other conditional knockouts (cKO) or double-deficient (DKO). Genotyping was performed as previously (Cavalheiro et al, 2014). …”

“…Eyes were enucleated, the length of axial ( x ), dorsal-ventral ( y ) and medial-lateral ( z ) axis were measured and volume was calculated as previously (Cavalheiro et al, 2014). Lenses dissected in phosphate-buffered saline (PBS) were similarly measured.…”

“…Previously, we characterized the physiological roles of c-myc in mouse lens development (Cavalheiro et al, 2014). Inactivation of c-myc in the surface ectoderm impaired lens growth and caused microphthalmia due to decreased cell proliferation.…”

p120-catenin-dependent junctional recruitment of Shroom3 is required for apical constriction during lens pit morphogenesis

“…This might be due to unidentified function(s) mediated by Shroom3 that are distinct from those involving p120-catenin. Several mouse mutants that display a similar lens stalk phenotype have disruptions in additional morphogenetic processes, such as proliferation, adhesion, differentiation and apoptosis, leaving open the possibility that Shroom3 might also function in these processes (Dimanlig et al, 2001;Ozeki et al, 2001;Medina-Martinez et al, 2005;Yoshimoto et al, 2005;Chen et al, 2008;Pontoriero et al, 2008Pontoriero et al, , 2009Kuracha et al, 2011;Cavalheiro et al, 2014).…”