Birc7: A Late Fiber Gene of the Crystalline Lens

Lens fiber cells are formed continuously by differentiation of cells at the edge of the lens epithelium. Newly formed cells are aligned on top of existing fiber cells, stacked like planks of wood in a lumber yard. The cell stacks (also referred to as radial cell columns1) arise deep in the tissue and extend to the surface of the lens. There is no cell turnover in the fiber cell compartment. Consequently, each stack contains a complete cellular record, with the oldest fibers at the base and the youngest on the top. All fiber cells are transparent and share an elongated prismatic shape. This has sometimes led to the assumption that they are a homogeneous population. In fact, depending on the relative positions of fibers in the cell stack, differences in biochemical or cell biological properties can be stark.2 For example, the basal tips of superficial fiber cells make direct contact with the posterior lens capsule. In contrast, older cells, located farther down the stack, have detached from the capsule and instead form connections with other fiber cells, in a region called the lens suture. Deep in the stack, fiber cells are deprived of oxygen, due to consumption by overlying cells.3 Consequently, the proportion of cellular ATP derived from oxidative phosphorylation differs markedly between the hypoxic inner cell layers and the relatively oxygenated outer fibers.4 Finally, a few hundred micrometers below the lens surface, fibers undergo programmed organelle destruction, whereby the nucleus and other membranous organelles are rapidly and synchronously degraded.5 The dissolution of the organelles ensures the removal of light-scattering structures and results in the formation of the central, organelle-free zone (OFZ) of the lens.6 Unlike the synthetically active surface cells, fiber cells within the OFZ lack the capacity for de novo protein synthesis.7 Based on such considerations it is likely that the biochemical differences between fibers located at different depths in the cell stack are as profound as those that exist between fiber cells and epithelial cells. Once fiber cells have begun the process of terminal differentiation, gene expression is adjusted continuously, so that the cell biology of a fiber is appropriate to its position in the stack. Of particular interest are genes expressed in cells bordering the OFZ. This set of “late fiber genes” is likely to include genes associated with the organelle degradation process or stabilizing the fiber cell phenotype. Founder members of this group of late fiber genes include Hopx,8 Capn3,9 Dnase2b (DLAD),10,11 and lengsin (Lgsn).12 Hopx is expressed in fiber cells that have lost their direct connection to the lens capsule.8 In keratinocytes, Hopx is expressed in the suprabasal layer, where it may control expression of differentiation-dependent genes. Capn3 encodes a calcium-activated endopeptidase, involved in remodeling of the spectrin cytoskeleton.13 Dnase2b is a lysosomal nuclease.11 It has been shown to mediate chromatin breakdown during organelle loss and its absence results in cortical cataract due to incomplete DNA removal.10 Lengsin is expressed in cells during the membrane remodeling phase and interacts directly with the intermediate filament proteins Cp49 and vimentin, perhaps facilitating cytoskeletal reorganization.12 To identify other late fiber genes, we used laser microdissection to harvest cells from various layers of the lens for comparative transcriptional analysis. We sought to identify genes that were expressed immediately prior to organelle breakdown. In this report, we characterized the expression of one such transcript, Livin (encoded by Birc7), which was strongly expressed in cells bordering the OFZ. Livin is an antiapoptotic protein (IAP) with suspected roles in progression of melanoma14 and other malignancies.15