Li H , Tierney C , Wen L , Wu JY , Rao Y .

R01 CA114197-01A2 NCI NIH HHS , R01 EY014576-03 NEI NIH HHS , R01 GM070967-02 NIGMS NIH HHS , R01 CA114197 NCI NIH HHS , R01 EY014576 NEI NIH HHS , R01 GM070967 NIGMS NIH HHS

	Fig. 1. Models for retina primordium formation in vertebrate embryos. The outline illustrates the boundary of the neural plate and the filled circles represent retina primordia. (A) The two separate retina primordia model. (B) A diagram of Stockard’s model of how a single primordium spreads and separates into two retinae. Some of Stockard’s results were directly contradicted by later studies of Adelmann (1929a,b). (C) This is essentially the same as Figs 1, 2 and 4 of LePlat (1919). (D) A schematic representation of Adelmann’s model. It was not determined whether midline cells could migrate laterally. (E) An illustration of the forebrain field model. Eyes are presumably the default fate of this field (Corner, 1966; Boterenbrood, 1970).
	Fig. 2. Alignment of the predicted primary sequence within the T domain of ET with those of other T domain proteins. A dash (-) indicates identity to Xbra. A period (.) indicates a gap. Residues shown in the consensus line are those identical in all known T domains while a star (*) indicates a highly but not absolutely conserved residue. Boxed residues are conserved only between ET and Omb. Omb is the predicted product of the Drosophila gene optomotor blind (Pflugfelderet al., 1992). Trg is that of the Drosophila T related gene involved in hindgut development (Kispert et al., 1994). T, Zf-T (or Ntl) and Xbra are the mouse, zebrafish and Xenopus T proteins respectively (Hermann et al., 1990; Smith et al., 1991; Schulte- Merker et al., 1992). Numbers for the ET sequence indicate positions predicted from the PCR fragment while numbers for known T domain proteins are positions in corresponding full-length proteins.
	Fig. 3. The expression pattern of ET in Xenopus embryos. A to G show anterior views and H is a lateral view. (A) A stage (st.) 12.5 embryo with a band of expression in the anterior neural plate (indicated by the arrow) and one in the primordium of the cement gland (indicated by the arrowhead). Note that the cement gland stays a single structure (A, C-G), whereas the retina band resolves into two primordia in the next few stages. (B) A st. 15 embryo showing retina field expression. The embryo was oriented to maximize visualization of retina expression and the cement gland is thus hardly visible. (C) A st. 16 embryo with ET expression weaker in the median region of the retina field than that in the lateral regions. (D) A st. 18 embryo with two distinct retina primordia. There is no ET expression in the median region. (E) A st. 19 embryo with no midline expression. (F) A st. 20 embryo. Note that weak expression of ET appears in the pineal gland primordium. The intensity of this signal increases in later stages (see G and H). (G) A st. 22 embryo with ET expression in the retina, the cement gland and the pineal gland (the dot between the two eyes). (H) A st. 26 embryo. The staining in the eye is restricted to the dorsal retina, absent from the lens and the ventral retina. Expression in the cephalic ganglia and lateral line organ also appeared. (I) A transverse section of a st. 28 embryo showing ET expression in the dorsal retina. ET is expressed in all layers of the retina, and completely absent from the lens. Dorsal is to the right.
	Fig. 4. Comparison of Pax-6 sequence from Xenopus with those from other species. Alignment of the predicted sequences of full-length Pax-6 proteins from Xenopus, mouse and human. A dash (-) indicates identity to the Xenopus sequence. The paired domain (amino acid residues 3-133) and homeo domain (residues 209-269) are in bold.
	Fig. 5. Distribution of Pax-6 mRNA in Xenopus embryos. A-G show anterior views, H is a dorsal view with the anterior end of the embryo to the left, and I is a lateral view. (A) A st. 12 embryo; note a single band of expression continuous from one side of the embryo to the other in the anterior neural plate (indicated by the red arrow) whereas there are two broad stripes of expression in the primordium of the neural tube (indicated by the red arrowhead). (B) A st. 12.5 embryo. The stripes in the trunk region are thinner and closer to each other than those at st. 12. Note the appearance of lens primordia on each side of the embryo (indicated by the green arrow). (C) A st. 16 embryo. The two red lines demarcate the borders of the retina stripe. The arrow points to a lens primordium. Pax-6 expression has three components: lens primordium, an outer semicircle of the retina field and an inner semicircle of a forebrain structure. The forebrain stripe later resolves into two spots posterior to the eyes shown in D and G, which are the two spots closer to the midline than the eyes in E and F. (D) A st. 18 embryo showing that Pax-6 expression in the median region of the anterior neural plate is turned off. The red line indicates the border between the eye primordium and the forebrain structure. Note also that the lens primordia have moved into the retina primordia to form the eye primordium by this stage (compare D to C). (E) A st. 19 embryo showing distinct Pax 6 expression in the eyes and the forebrain. (F) A stage 26 embryo. (G) Higher magnification of a st. 18 embryo. The line points to the border between the forebrain staining and the eye staining. (H) Dorsal view of a st. 24 embryo showing Pax-6 expression in the neural tube derived from the two broad stripes in the trunk region at st. 12 (the arrowhead in A). (I) A st. 25 embryo. Compare Pax-6 expression in the entire eye to ET expression in only the dorsal retina in Fig. 3H.
	Fig. 6. Fate mapping of midline cells in the retina field of Xenopus embryos. A to D show anterior views. (A) A diagram showing that midline cells in the retina field were labeled by DiI at stages 12 or 12.5 and followed to stage 25 to determine whether the midline cells migrate to the lateral regions. (B) The original location of DiI-labeled cells. This embryo was labeled with DiI at stage 12 and fixed at stage 12.5. DiI was photoconverted to produce the brown spot in the middle of the retina field, which was revealed by in situ hybridization with the Xenopus Pax-6 probe. (C) An image of a stage 25 embryo illuminated by incident light. A yellow arrow points to an eye. (D) A composite of the image shown in C and an image of the same embryo viewed under rhodamine optics to map the location of the fluorescent cells. A yellow arrow points to an eye. This embryo was previously labeled with DiI at stage 12.5. Results were similar with embryos labeled at stage 12. (E) A left side view of another DiI-labeled embryo. Note the absence of DiI labeled cells in the left retina. A white arrow points to DiI-labeled cells. A yellow arrow points to an eye.
	Fig. 7. Effects of removing the prechordal mesoderm on retina formation in Xenopus embryonic explants. (A) A wild-type embryo at st. 35. (B) A st. 35 control explant of the anterior neural plate with the underlying prechordal mesoderm. (C) An anterior neural plate explant without prechordal mesoderm. The explants were isolated at st. 12.5 and cultured until st. 35. (D) A transverse section of a st. 42 control explant after in situ hybridization with a Pax-6 probe. (E) A transverse section of a st. 42 explant without prechordal mesoderm at st. 12.5 and fixed for in situ hybridization with Pax-6 at st. 42. Note the presence of Pax-6 expressing neural retina as well as the retina pigment epithelium.
	Fig. 8. Effects of prechordal mesoderm removal on retina field resolution in Xenopus embryonic explants. (A) A control embryo hybridized with Pax-6 at st. 18. (B) Pax-6 expression in a control anterior neural plate explant with the underlying mesoderm, showing two separate primordia by st. 18. (C) Pax-6 expression in a st. 18 explant of the anterior neural plate without the underlying mesoderm. Note the retina field did not resolve into two separate primordia. (D) A control embryo hybridized with ET at st. 18. (E) ET expression in a st. 18 control explant with the prechordal mesoderm. (F) ET expression in a st. 18 explant without prechordal mesoderm.
	Fig. 11. Retina primordium formation in vertebrate embryos. (A) Our model of retina field development. Dorsal views of the anterior neural plate are illustrated here. There is initially a single retina morphogenetic field in the anterior neural plate of vertebrate embryos. Retina formation is suppressed in its median region, resulting in the resolution of the retina field into two retina primordia. (B) The prechordal plate provides a primary signal for retina field resolution. These are transverse section views of the anterior neural plate and its underlying prechordal mesoderm. Experiments reported here demonstrate a role for the prechordal plate while those performed in zebrafish embryos suggest the midline of the neural plate also plays a role (Hatta et al., 1991, 1994; Hatta, 1992; Macdonald et al., 1995; Ekker et al., 1995b).

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