A TRANSIENT ROLE FOR CILIARY NEUROTROPHIC FACTOR IN CHICK PHOTORECEPTOR DEVELOPMENT

Previous studies suggest that ciliary neurotrophic factor (CNTF) may r epresent one of the extrinsic signals controlling the development of v ertebrate retinal photoreceptors, In dissociated cultures from embryon ic chick retina, exogenously applied CNTF has been shown to act on pos tmitotic rod precursor cells, resulting in an two- to fourfold increas e in the number of cells acquiring an opsin-positive phenotype, We now demonstrate that the responsiveness of photoreceptor precursors to CN TF is confined to a brief phase between their final mitosis and their terminal differentiation owing to the temporally restricted expression of the CNTF receptor (CNTFR alpha). As shown immunocytochemically, CN TFR alpha expression in the presumptive photoreceptor layer of the chi ck retina starts at embryonic day 8 (E8) and is rapidly down-regulated a few days later prior to the differentiation of opsin-positive photo receptors, both in vivo and in dissociated cultures from E8, We furthe r show that the CNTF-dependent in vitro differentiation of rods is fol lowed by a phase of photoreceptor-specific apoptotic cell death, The l oss of differentiated rods during this apoptotic phase can be prevente d by micromolar concentrations of retinol, Our results provide evidenc e that photoreceptor development depends on the sequential action of d ifferent extrinsic signals, The time course of CNTFR alpha expression and the in vitro effects suggest that CNTF or a related molecule is re quired during early stages of rod differentiation, while differentiate d rods depend on additional protective factors for survival. (C) 1998 John Wiley & Sons, Inc.