[Mechanisms of retinal photoreceptor cell fate determination].
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Nishida
Akihiro
A
Department of Developmental Biology, Osaka Bioscience Institute, 6 2-4, Furuedai, Suita 565-0874, Japan. nishida@obi.or.jp
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D051857:Otx Transcription Factors / Q000235:genetics*; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology*; D010870:Pineal Gland; D015534:Trans-Activators / Q000235:genetics
D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D015534:Trans-Activators; C109288:cone rod homeobox protein