Conversion of iris epithelial cells as a model of differentiation control.

It has been shown that, upon lentectomy or in culture, iris epithelial cells (IECs) of adult newts become converted into lens cells, and this conversion is the basic event of lens regeneration in newts. Whether in situ or in cell culture, the conversion requires the passage of a specific number of cell cycles. The progeny of IECs which fails to traverse this cell-cycle number redifferentiates as IECs in situ. The passage through cell cycles of IECs is associated with progressive alterations of cytoplasm and cell surface, during which the original state of differentiation disappears (dedifferentiation). It is speculated that the altered state of cells caused by proliferation leads to the appearance of factors which interact with the genome and switch the gene activation pattern to that of the lens cell. In this model, developmental controls are geared to the cell-cycle progression and not directly to the activation of lens-characteristic genes. A number of points are raised which speak against the long-held idea that a factor from neural retina induces lens differentiation in IECs. It is proposed that the retinal factor plays the role of growth factor which is essential in the conversion in situ, but not required in the conversion in cell culture. The proposed model is compared with reprogramming of differentiation of some cell lines by cytidine analogs and with ontogenic systems of differentiation control.