Tang K , Tsai SY , Tsai MJ .

P01 DK059820 NIDDK NIH HHS , R01 DK045641 NIDDK NIH HHS , U19 DK062434 NIDDK NIH HHS , R01 HL076448 NHLBI NIH HHS , HL114539 NHLBI NIH HHS , R01 DK45641 NIDDK NIH HHS , P30 DK079638 NIDDK NIH HHS , DK079638 NIDDK NIH HHS , R01 HL114539 NHLBI NIH HHS

Fig. 1. Molecular mechanisms of COUP-TF action. (top panel) COUP-TFs repress gene expression by directly binding to the DR (direct repeat) site of the gene, such as Pax6 in the eye [19] (Table 1). (Bottom panel) COUP-TFs activate gene expression through forming a modulatory complex with the Sp1 transcription factor, which binds at the Sp1 site of the gene, such as Otx2 in the eye [19] (Table 2).

Fig. 2. COUP-TF genes and eye development. (A) The expression of COUP-TFs and other key regulators in four domains of the early optic vesicle. Along the dorso-distal and ventro-proximal axis of the early optic vesicle, COUP-TFs are expressed highest in the pdOS, highly in the pRPE, and relatively low in the ventral pNR and pvOS. (B) COUP-TFs are necessary for the differentiation of dOS. (C) COUP-TFs are crucial determinants for the RPE identity. (D) COUP-TFs and the formation of the NR-vOS boundary. dOS, dorsal optic stalk; NR, neural retina; pdOS, presumptive dorsal optic stalk; pNR, presumptive neural retina; pRPE, presumptive retinal pigmented epithelium; pvOS, presumptive ventral optic stalk; vOS, ventral optica stalk.

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