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[Mechanisms of retinal photoreceptor cell fate determination].

PURPOSE
Understanding the molecular mechanisms by which distinct cell fate is determined during organogenesis is a central issue in cell development and disease. Using conditional gene ablation, we show that in mice the transcription factor Otx2 is essential for retinal photoreceptor cell fate determination and the development of the pineal gland.


METHODS AND RESULTS
In the Otx2 knockout mice, differentiating photoreceptor cells were converted to amacrine-like neurons, and the pinealocytes in the pineal gland were totally absent. In addition, promoter assays revealed that Otx2 transactivates Crx, which is required for terminal differentiation and maintenance of photoreceptor cells. Furthermore, retroviral gene transfer of Otx2 steered retinal progenitor cells toward becoming photoreceptors.


CONCLUSION
Thus, Otx2 is a key regulatory gene for the cell fate determination of retinal photoreceptor cells. Our results revealed the key molecular steps required for photoreceptor cell fate determination and pineal gland development.