POSTMITOTIC CELLS FATED TO BECOME ROD PHOTORECEPTORS CAN BE RESPECIFIED BY CNTF TREATMENT OF THE RETINA

Lineage analyses of vertebrate retinae have led to the suggestions tha t cell fate decisions are made during or after the terminal cell divis ion and that extrinsic factors can influence fate choices. The evidenc e for a role of extrinsic factors is strongest for development of rode nt rod photoreceptors ('rods'). In an effort to identify molecules tha t may regulate rod development, a number of known factors were assayed in vitro. Ciliary neurotrophic factor (CNTF) was found to have a rang e of effects on retinal cells. Addition of CNTF to postnatal rat retin al explants resulted in a dramatic reduction in the number of differen tiating rods. Conversly, the number of cells expressing markers of bip olar cell differentiation was increased to a level not normally seen i n vivo or in vitro. In addition, a small increase in the percentage of cells expressing either a marker of amacrine cells or a marker of Mul ler glia was noted. It was determined that many of the cells that woul d normally differentiate into rods were the cells that differentiated as bipolar cells in the presence of CNTF. Prospective rod photorecepto rs could make this change even when they were postmitotic, indicating that at least a subset of cells fated to be rods were not committed to this fate at the time they were born. These findings highlight the di stinction between cell fate and commitment. Resistance to the effect o f CNTF on rod differentiation occurred at about the time that a cell b egan to express opsin. The time of commitment to terminal rod differen tiation may thus coincide with the initiation of opsin expression. In agreement with the hypothesis that CNTF plays a role in rod differenti ation in vivo, a greater percentage of cells were observed differentia ting as rod photoreceptors in mouse retinal explants lacking a functio nal CNTF receptor, relative to wild-type littermates.