Abstract
Optical function in the zebrafish lens is similar to the adult human lens and is largely determined by the constraints of the physical properties of light. While development in zebrafish does not include formation of a lens vesicle, a symmetric, refractile, transparent lens is generated from a sheet of undifferentiated, embryonic, cranial epithelium using biological mechanisms that are similar to human lens development. Proliferation, migration and elongation of surface cells establish a spherical cellular mass in which polarization and reorganization of cells produce a functional optical element, the lens of the eye. Two-photon live-embryo imaging was used to record individual cells in real-time and define a fate map for lens cells during development from the placode to the functional lens. Cells were followed from the placode stage through morphological differentiation. Cells destined to become epithelial or primary fiber cells followed predictable but separate paths of migration during development. Cells in the peripheral lens placode migrated to the anterior lens mass and differentiated into an anterior epithelium. Cells in the central lens placode migrated to the posterior lens mass and differentiated into primary fiber cells. Anterior and posterior polarization in the zebrafish lens cell mass was similar to anterior and posterior polarization in the mammalian lens vesicle. Fiber cell differentiation began prior to separation of the lens mass from the surface ectoderm, as evidenced by cell elongation, exit from the cell cycle, and expression of Zl-1, a lens fiber cell marker. TUNEL labeling demonstrated that apoptosis was not a primary mechanism for separation of the lens from the surface ectoderm and future cornea. BrdU incorporation revealed that proliferation was restricted to a lateral zone in the anterior epithelium. We conclude that the symmetry, refraction and transparency necessary for image formation in the visual system requires a high degree of synchrony in specifying the fates of individual cells and their symmetrical, spatial relationships in the adult lens. In lens, developmental defects are extremely rare suggesting unique intersecting, developmental pathways that protect against the deleterious effects of cell and molecular aging. Lens development is complex and highly coordinated and cellular mechanisms for lens organogenesis are conserved throughout vertebrates.