Degeneration of photoreceptors is a consistent and common endpoint in retinal diseases. Herein, we report the efficient induction of photoreceptor-like cells front Mouse embryonic stem (ES) cells using chick embryonic retina tissue. Undifferentiated mouse ES cells were initially cultured in a preferential condition into a neural lineage, and ES cells were then co-cultured with chick embryonic day 6 (E6) retina tissues. After a 10-day co-culture, approximately 20% of the mouse ES derivatives became immuno-positive for rhodopsin. RT-PCR analysis demonstrated expression of the transcription factor crx and a distinct increase of rod photoreceptor-specific markers, IRBP and recoverin, after the start of the co-culture. These results indicate that co-culture of ES cells with chick embryonic retina tissue is a useful and efficient method for the induction of photoreceptor-like cells. (c) 2005 Elsevier Inc. All rights reserved.