Bone morphogenetic protein 7 increases chick photoreceptor outer segment initiation

PURPOSE. The purpose of this study was to investigate the regulation of photoreceptor differentiation and outer segment elongation by the growth factor BMP7. METHODS. Dissociated low-density embryonic day 6 (E6) chick retinal cultures were grown for 6 days in the presence of BMP7, other members of the TGF-beta family of growth factors, or control vehicle. Cultured cells were characterized using microscopy, immunocytochemistry, and RT-PCR. Antibodies against visinin and GABA were used to distinguish photoreceptors from nonphotoreceptor cells, and monoclonal antibodies rhodopsin ( rho) 4D2, OS-2, and COS-1 were used to distinguish subpopulations of cones and rods. RT-PCR was used to investigate mRNAs encoding visual pigments. RESULTS. Photoreceptors treated with BMP7 initiated outer segment elongation more frequently than photoreceptors in control cultures. The effect on outer segment initiation was confined to rods and to green opsin-expressing cones and appeared not to involve an increase in outer segment length. BMP7 did not appear to affect the survival, proliferation, or differentiation of progenitors or the fate of photoreceptors or amacrine cells in vitro. BMP5 and GDF5 showed weaker stimulatory effects than BMP7 on outer segment formation, whereas activin, BMP2, and BMP4 inhibited visual pigment expression and outer segment formation, and BMP6 had no detectable effects. CONCLUSIONS. BMP7 must be added to the list of candidate molecules capable of stimulating outer segment formation.