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. 2015 Jan;185(1):197–213. doi: 10.1016/j.ajpath.2014.09.002

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© 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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Conditional Porcn inactivation in ocular and neural crest–derived mesenchyme induces pigment abnormalities and transdifferentiation of the retinal pigment epithelium (RPE) at E15.5. A–D: Lateral views of WT (A), Porcn^lox/Y;Wnt1-Cre (B), Porcn^lox/Y;Rx3-Cre (C), and Porcn^lox/Y;Wnt1-Cre;Rx3-Cre embryos (D). E: WT eye. F–H: Range of severities of ocular phenotypes found in Porcn^lox/Y;Wnt1-Cre;Rx3-Cre embryos: colobomata (arrowhead) with largely circumferential pigment loss (F, arrow); more severe pigment loss dorsally (G); or, in rare cases, completely absent pigment (H). I–T: Coronal views. I and K: Expression of HES1 (red) in retinal progenitor cells and BRN-3 (green) in differentiating ganglion cells in WT retina, with WT ventral optic cup shown at higher magnification (K). J: In Porcn^lox/Y;Wnt1-Cre;Rx3-Cre retina, expression of HES1 and BRN-3 shows a normal distribution. L: Higher magnification of the Porcn^lox/Y;Wnt1-Cre;Rx3-Cre ventral optic cup reveals ectopic up-regulation of HES1 and BRN-3 in the RPE (arrow). The dotted line marks the apical borders of retina and transdifferentiated RPE; note optic stalk (asterisk) and reduced vitreous (arrowhead). M and O: Expression of OTX2 (green) in retinal progenitors and photoreceptor precursors and of VSX2 (red) in retinal progenitors in WT retina, with ventral optic cup shown at higher magnification (O). N: Expression of OTX2 and VSX2 appears normal in Porcn^lox/Y;Wnt1-Cre;Rx3-Cre retina. P: Higher magnification of the Porcn^lox/Y;Wnt1-Cre;Rx3-Cre ventral optic cup reveals ectopic up-regulation of VSX2 and retinal OTX2 expression in the RPE (arrow); the dotted line marks the apical borders of retina and transdifferentiated RPE; note optic stalk (asterisk) and reduced vitreous (arrowhead). Q: LEF1 expression in WT retina. R: In Porcn^lox/Y;Wnt1-Cre;Rx3-Cre embryos, LEF1 is down-regulated in the dorsal and ventral optic cup periphery (arrowheads) and in the ventral eyelid mesenchyme (asterisk). S: p-JUN expression in WT retina and lens. T: p-JUN in Porcn^lox/Y;Wnt1-Cre;Rx3-Cre embryos appears normal. Scale bars: 1 mm (A and H); 200 μm (E); 100 μm (I, K, M, O, Q, and S).