SIX3, A MEDAKA HOMOLOG OF THE DROSOPHILA HOMEOBOX GENE SINE OCULIS ISEXPRESSED IN THE ANTERIOR EMBRYONIC SHIELD AND THE DEVELOPING EYE

The conserved transcription factor Pax6 is essential for eye developme nt in Drosophila and mammals (Hill, R.E., Favor, J., Hogan, B.L.M., To n, C.C.T., Saunders, G.F., Hanson, I.M., Presser, J., Jordan, T., Hast ie, N.D., van Heyningen, V., 1991. Mouse small eye results from mutati ons in a paired-like homeobox containing gene. Nature 354, 522-525; To n, C., Hirvonen, H., Miwa, H., Well, M., Monaghan, P., Jordan, T., van Heyningen, V., Hastie, N., Meijers-Heijboer, H., Drechsler, M., Royer -Pokora, B., Collins, F., Swaroop, A., Strong, L.C., Saunders, G.F., 1 991. Positional cloning and characterization of a paired box- and home obox-containing gene from the aniridia region. Cell 6, 1059-1074; Mats uo, T., Osumi-Yamashita, N., Noji, S., Ohuchi, Fl., Koyama, E., Myokai , F., Matsuo, N., Toniguchi, S., Dari, H., Jseki, S., Ninomiya, Y., Fu jiwara, hi., Watanabe, T., Eto, K., 1993. A mutation at the Pax-6 gene in rat small eye is associated with impaired migration of midbrain cr est cells. Nature Genet. 3, 299-304; Quiring, R., Walldorf, U., Kloter , U., Gehring, W.J., 1994. Homology of the eyeless gene of Drosophila to the small eye gene in mice and aniridia in humans. Science 265, 785 -789). These findings led to the hypothesis that additional genes invo lved in invertebrate and vertebrate eye development are structurally a nd functionally conserved (Halder, G., Callaerts, P., Gehring, W.J., 1 995. New perspectives on eye evolution. Curr. Opin. Cen. Dev. 5, 602-6 09; Quiring, R., Walldorf, U., Kloter, U., Gehring, W.J., 1993. Homolo gy of the eyeless gene of Drosophila to the small eye gene in mice and aniridia in humans. Science 265, 785-789). Candidates for such conser ved genes are the Drosophila homeobox gene sine oculis (Cheyette, B.N. R., Green, P.J., Martin, K., Garren, H., Hartenstein, V., Zipursky, S. L., 1994. The Drosophila sine oculis locus encodes a homeodomain-conta ining protein required for the development of the entire visual system . Neuron 12, 977-996) and its murine homologue Six3 (Oliver, G., Mailh os, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3 , a murine homologue of the sine oculis gene, demarcates the most ante rior border of the developing neural plate and is expressed during eye development. Development 121, 4045-4055). sine oculis (SO) is essenti al for the development of the larval and adult visual system (Cheyette , B.N.R., Green, P.J., Martin, K., Garren, H., Hartenstein, V., Zipurs ky, S.L., 1994. The Drosophila sine oculis locus encodes a homeodomain -containing protein required for the development of the entire visual system. Neuron 12, 977-996). Six3 is expressed in the anterior neural plate and optic vesicles, lens, olfactory placodes and ventral forebra in (Oliver, G., Mailhos, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a murine homologue of the sine oculis gene, dem arcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121, 4045-4055). Overex pression of mouse Six3 gene in medaka fish embryos (Orvzias latipes) r esults in the formation of an ectopic lens, indicating that Six3 activ ity can trigger the genetic pathway leading to lens formation (Oliver, G., Loosli, F., Koster, R., Wittbrodt, J., Gruss, P., 1996. Ectopic l ens induction in fish in response to the murine homeobox gene Six3. Me ch. Dev. 60, 233-239. We isolated the medaka Six3 homologue and analyz ed its expression pattern in the medaka embryo. It is expressed initia lly in the anterior embryonic shield and later in the developing eye a nd prosencephalon. The early localized expression of Six3 suggests a r ole in the regionalization of the rostral head. (C) 1998 Elsevier Scie nce Ireland Ltd. All rights reserved.