EARLY EMBRYONIC INTERACTION OF RETINAL-PIGMENT EPITHELIUM AND MESENCHYMAL TISSUE INDUCES CONVERSION OF PIGMENT-EPITHELIUM TO NEURAL RETINALFATE IN THE SILVER MUTATION OF THE JAPANESE-QUAIL

The neural retina and retinal pigment epithelium (RPE) diverge from th e optic vesicle during early embryonic development. They originate fro m different portions of the optic vesicle, the more distal part develo ping as the neural retina and the proximal part as RPE. AS the distal part appears to make contact with the epidermis and the proximal part faces mesenchymal tissues, these two portions would encounter differen t environmental signals. In the present study, an attempt has been mad e to investigate the significance of interactions between the RPE and mesenchymal tissues that derive from neural crest cells, using a uniqu e quail mutant silver (B/B) as the experimental model. The sliver muta tion is considered to affect neural crest-derived tissues, including t he epidermal melanocytes. The homozygotes of the silver mutation have abnormal eyes, with double neural retinal layers, as a result of aberr ant differentiation of RPE to form a new neural retina. Retinal pigmen t epithelium was removed from early embryonic eyes (before the process began) and cultured to see whether it expressed any phenotype charact eristic of neural retinal cells. When RPE of the B/B mutant was cultur ed with surrounding mesenchymal tissue, neural retinal cells were diff erentiated that expressed markers of amacrine, cone or rod cells. When isolated RPE of the B/B mutant was cultured alone, it acquired pigmen tation and did not show any properly characteristic of neural retinal cells. The RPE of wild type quail always differentiated to pigment epi thelial cells. In the presence of either acidic fibroblast growth fact or (aFGF) or basic FGF (bFGF), the RPE of the B/B mutant differentiate d to neural retinal cells in the absence of mesenchymal tissue, but th e RPE of wild type embryos only did so in the presence of 10-40 times as much aFGF or bFGF. These observations indicate that genes responsib le for the B/B mutation are expressed in the RPE as well as in those c ells that have a role in the differentiation of neural crest cells. Th ey further suggest that development of the neural retina and RPE is re gulated by some soluble factor(s) that is derived from or localized in the surrounding embryonic mesenchyme and other ocular tissues, and th at FGF may be among possible candidates.