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Fig. 6. Effects of interfering with BMP signalling on the distribution of transcripts known to be involved in NR and RPE development. (A) Mitf expression in the contralateral, untreated eye following implantation of noggin-expressing CHO cells. Mitf expression is restricted to the RPE (arrowhead). (B) Inhibition of BMP signalling downregulates Mitf expression in the outer optic cup (arrowheads) and only a small single-layered region still expresses Mitf (arrows). (C) MMP115 expression in the contralateral, untreated eye following implantation of noggin-expressing cells. MMP115 transcripts are restricted to the RPE. (D) Parallel section of the noggin-treated eye shown in B. MMP115 expression is downregulated in the outer optic cup (arrowheads), although MMP115 expression is still maintained in a small region that still has RPE-like morphology (arrow). (E) Following implantation of noggin-expressing CHO cells, the single-layered RPE suddenly thickens in the proximal region of the eye (arrow). Pigmentation is still observed in the unaffected areas of the RPE (arrowheads). (F) Higher magnification of the eye shown in E. The RPE is pigmented (arrowhead), whereas the adjacent multilayered area is unpigmented (arrow). (G) Parallel section of the noggin-treated eye shown in E and F. Rx expression is observed in the native NR and in the outer optic cup that has NR-like morphology (arrow). Expression is absent in the single-layered RPE (arrowhead). (H) Proximal region of a noggin-treated eye at stage 25. At this stage, Pax6 expression is strongly detected in the native NR, whereas transcripts are absent from the pigmented single-layered RPE (see also arrowhead in I). Following noggin treatment, strong Pax6 expression is induced in a small, multilayered region of the outer layer of the optic cup (box). The arrowhead indicates weak Pax6 expression in the RPE. Note that Pax6 expression is also observed in the brain on the right side. (I) Higher magnification of the multilayered region in the outer optic cup shown in H. This region strongly expresses Pax6 (arrow), whereas expression is not observed in the single-layered, pigmented RPE (arrowhead). (J) Parallel section of the eye shown in H and I. MMP115 expression is downregulated in the Pax6-expressing region that is multilayered (arrow).

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