GENETIC-CHARACTERIZATION OF THE MULTIPOTENT DEDIFFERENTIATED STATE OFPIGMENTED EPITHELIAL-CELLS IN-VITRO

Retinal pigmented epithelial cells (PECs) of chicken embryos extensive ly and almost synchronously transdifferentiate into lens cells in medi um containing phenylthiourea and testicular hyaluronidase, passing thr ough the bipotent dedifferentiated state. We have isolated genes that are expressed specifically by either pigment or lens cells and analyze d their expression in the transdifferentiation process. The expression of some proto-oncogenes was also studied. In the dedifferentiation pr ocess, expression of the c-myc gene was enhanced and the transcription of PEC-specific genes (MMP115, pP344) was completely repressed. Howev er, transcription of lens-specific genes (alpha-, beta- and delta-crys tallin genes) remained silent in dedifferentiated pigment cells. Activ ation of lens- or PEC-specific genes occurred only in conditions permi ssive for lens or PEC differentiation, respectively. These results ind icated that lens transdifferentiation from PECs proceeds through a mul tipotent (or at least bipotent) intermediate cell state in which the c -myc gene is activated, but neither PEC- nor lens-specific genes are e xpressed.