Crim1 is required for maintenance of the ocular lens epithelium

Abstract

The development and growth of the vertebrate ocular lens is dependent on the regulated proliferation of an anterior monolayer of epithelial cells, and their subsequent differentiation into elongate fiber cells. The growth factor rich ocular media that bathes the lens mediates these cellular processes, and their respective intracellular signaling pathways are in turn regulated to ensure that the proper lens architecture is maintained. Recent studies have proposed that Cysteine Rich Motor Neuron 1 (Crim1), a transmembrane protein involved in organogenesis of many tissues, might influence cell adhesion, polarity and proliferation in the lens by regulating integrin-signaling. Here, we characterise the lens and eyes of the Crim1^KST264 mutant mice, and show that the loss of Crim1 function in the ocular tissues results in inappropriate differentiation of the lens epithelium into fiber cells. Furthermore, restoration of Crim1 levels in just the lens tissue of Crim1^KST264 mice is sufficient to ameliorate most of the dysgenesis observed in the mutant animals. Based on our findings, we propose that tight regulation of Crim1 activity is required for maintenance of the lens epithelium, and its depletion leads to ectopic differentiation into fiber cells, dramatically altering lens structure and ultimately leading to microphthalmia and aphakia.

Keywords: Crim1; Fiber differentiation; Lens epithelium; Lens fibers; TGFβ.