Abstract
The glass gene encodes a zinc finger, DNA-binding protein that is required for photoreceptor cell development in Drosophila melanogaster. In the developing compound eye, glass function is regulated at two points: (1) the protein is expressed in all cells' nuclei posterior to the morphogenetic furrow and (2) the ability of the Glass protein to regulate downstream genes is largely limited to the developing photoreceptor cells. We conducted a series of genetic screens for autosomal dominant second-site modifiers of the weak allele glass(3), to discover genes with products that may regulate glass function at either of these levels. Seventy-six dominant enhancer mutations were recovered (and no dominant suppressors). Most of these dominant mutations are in essential genes and are associated with recessive lethality. We have assigned these mutations to 23 complementation groups that include multiple alleles of Star and hedgehog as well as single alleles of Delta, roughened eye, glass and hairy. Mutations in 18 of the complementation groups are embryonic lethals, and of these, 13 show abnormal adult retinal phenotypes in homozygous clones, usually with altered numbers of photoreceptor cells in some of the ommatidia.
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- Agnel M., Kerridge S., Vola C., Griffin-Shea R. Two transcripts from the rotund region of Drosophila show similar positional specificities in imaginal disc tissues. Genes Dev. 1989 Jan;3(1):85–95. doi: 10.1101/gad.3.1.85. [DOI] [PubMed] [Google Scholar]
- Alton A. K., Fechtel K., Kopczynski C. C., Shepard S. B., Kooh P. J., Muskavitch M. A. Molecular genetics of Delta, a locus required for ectodermal differentiation in Drosophila. Dev Genet. 1989;10(3):261–272. doi: 10.1002/dvg.1020100315. [DOI] [PubMed] [Google Scholar]
- Baker N. E., Mlodzik M., Rubin G. M. Spacing differentiation in the developing Drosophila eye: a fibrinogen-related lateral inhibitor encoded by scabrous. Science. 1990 Dec 7;250(4986):1370–1377. doi: 10.1126/science.2175046. [DOI] [PubMed] [Google Scholar]
- Baker N. E., Moses K., Nakahara D., Ellis M. C., Carthew R. W., Rubin G. M. Mutations on the second chromosome affecting the Drosophila eye. J Neurogenet. 1992 May;8(2):85–100. doi: 10.3109/01677069209084154. [DOI] [PubMed] [Google Scholar]
- Baker N. E., Rubin G. M. Effect on eye development of dominant mutations in Drosophila homologue of the EGF receptor. Nature. 1989 Jul 13;340(6229):150–153. doi: 10.1038/340150a0. [DOI] [PubMed] [Google Scholar]
- Baker N. E., Zitron A. E. Drosophila eye development: Notch and Delta amplify a neurogenic pattern conferred on the morphogenetic furrow by scabrous. Mech Dev. 1995 Feb;49(3):173–189. doi: 10.1016/0925-4773(94)00314-d. [DOI] [PubMed] [Google Scholar]
- Barinaga M. Focusing on the eyeless gene. Science. 1995 Mar 24;267(5205):1766–1767. doi: 10.1126/science.7892596. [DOI] [PubMed] [Google Scholar]
- Basler K., Yen D., Tomlinson A., Hafen E. Reprogramming cell fate in the developing Drosophila retina: transformation of R7 cells by ectopic expression of rough. Genes Dev. 1990 May;4(5):728–739. doi: 10.1101/gad.4.5.728. [DOI] [PubMed] [Google Scholar]
- Begemann G., Michon A. M., vd Voorn L., Wepf R., Mlodzik M. The Drosophila orphan nuclear receptor seven-up requires the Ras pathway for its function in photoreceptor determination. Development. 1995 Jan;121(1):225–235. doi: 10.1242/dev.121.1.225. [DOI] [PubMed] [Google Scholar]
- Bier E., Ackerman L., Barbel S., Jan L., Jan Y. N. Identification and characterization of a neuron-specific nuclear antigen in Drosophila. Science. 1988 May 13;240(4854):913–916. doi: 10.1126/science.3129785. [DOI] [PubMed] [Google Scholar]
- Blair S. S. Compartments and appendage development in Drosophila. Bioessays. 1995 Apr;17(4):299–309. doi: 10.1002/bies.950170406. [DOI] [PubMed] [Google Scholar]
- Bonini N. M., Leiserson W. M., Benzer S. The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye. Cell. 1993 Feb 12;72(3):379–395. doi: 10.1016/0092-8674(93)90115-7. [DOI] [PubMed] [Google Scholar]
- Botas J., Moscoso del Prado J., García-Bellido A. Gene-dose titration analysis in the search of trans-regulatory genes in Drosophila. EMBO J. 1982;1(3):307–310. doi: 10.1002/j.1460-2075.1982.tb01165.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown N. L., Sattler C. A., Paddock S. W., Carroll S. B. Hairy and emc negatively regulate morphogenetic furrow progression in the Drosophila eye. Cell. 1995 Mar 24;80(6):879–887. doi: 10.1016/0092-8674(95)90291-0. [DOI] [PubMed] [Google Scholar]
- Bumcrot D. A., Takada R., McMahon A. P. Proteolytic processing yields two secreted forms of sonic hedgehog. Mol Cell Biol. 1995 Apr;15(4):2294–2303. doi: 10.1128/mcb.15.4.2294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cagan R. L., Ready D. F. Notch is required for successive cell decisions in the developing Drosophila retina. Genes Dev. 1989 Aug;3(8):1099–1112. doi: 10.1101/gad.3.8.1099. [DOI] [PubMed] [Google Scholar]
- Carthew R. W., Neufeld T. P., Rubin G. M. Identification of genes that interact with the sina gene in Drosophila eye development. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11689–11693. doi: 10.1073/pnas.91.24.11689. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chang D. T., López A., von Kessler D. P., Chiang C., Simandl B. K., Zhao R., Seldin M. F., Fallon J. F., Beachy P. A. Products, genetic linkage and limb patterning activity of a murine hedgehog gene. Development. 1994 Nov;120(11):3339–3353. doi: 10.1242/dev.120.11.3339. [DOI] [PubMed] [Google Scholar]
- Concordet J. P., Ingham P. Developmental biology. Patterning goes sonic. Nature. 1995 May 25;375(6529):279–280. doi: 10.1038/375279a0. [DOI] [PubMed] [Google Scholar]
- Dequin R., Saumweber H., Sedat J. W. Proteins shifting from the cytoplasm into the nuclei during early embryogenesis of Drosophila melanogaster. Dev Biol. 1984 Jul;104(1):37–48. doi: 10.1016/0012-1606(84)90034-4. [DOI] [PubMed] [Google Scholar]
- Dickson B., Hafen E. Genetics of signal transduction in invertebrates. Curr Opin Genet Dev. 1994 Feb;4(1):64–70. doi: 10.1016/0959-437x(94)90092-2. [DOI] [PubMed] [Google Scholar]
- Dietrich U., Campos-Ortega J. A. The expression of neurogenic loci in imaginal epidermal cells of Drosophila melanogaster. J Neurogenet. 1984 Dec;1(4):315–332. doi: 10.3109/01677068409107094. [DOI] [PubMed] [Google Scholar]
- Echelard Y., Epstein D. J., St-Jacques B., Shen L., Mohler J., McMahon J. A., McMahon A. P. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 1993 Dec 31;75(7):1417–1430. doi: 10.1016/0092-8674(93)90627-3. [DOI] [PubMed] [Google Scholar]
- Ekker S. C., Ungar A. R., Greenstein P., von Kessler D. P., Porter J. A., Moon R. T., Beachy P. A. Patterning activities of vertebrate hedgehog proteins in the developing eye and brain. Curr Biol. 1995 Aug 1;5(8):944–955. doi: 10.1016/s0960-9822(95)00185-0. [DOI] [PubMed] [Google Scholar]
- Ellis M. C., O'Neill E. M., Rubin G. M. Expression of Drosophila glass protein and evidence for negative regulation of its activity in non-neuronal cells by another DNA-binding protein. Development. 1993 Nov;119(3):855–865. doi: 10.1242/dev.119.3.855. [DOI] [PubMed] [Google Scholar]
- Ellis M. C., Weber U., Wiersdorff V., Mlodzik M. Confrontation of scabrous expressing and non-expressing cells is essential for normal ommatidial spacing in the Drosophila eye. Development. 1994 Jul;120(7):1959–1969. doi: 10.1242/dev.120.7.1959. [DOI] [PubMed] [Google Scholar]
- Fujita S. C., Zipursky S. L., Benzer S., Ferrús A., Shotwell S. L. Monoclonal antibodies against the Drosophila nervous system. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7929–7933. doi: 10.1073/pnas.79.24.7929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halder G., Callaerts P., Gehring W. J. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science. 1995 Mar 24;267(5205):1788–1792. doi: 10.1126/science.7892602. [DOI] [PubMed] [Google Scholar]
- Hazelrigg T., Levis R., Rubin G. M. Transformation of white locus DNA in drosophila: dosage compensation, zeste interaction, and position effects. Cell. 1984 Feb;36(2):469–481. doi: 10.1016/0092-8674(84)90240-x. [DOI] [PubMed] [Google Scholar]
- Heberlein U., Hariharan I. K., Rubin G. M. Star is required for neuronal differentiation in the Drosophila retina and displays dosage-sensitive interactions with Ras1. Dev Biol. 1993 Nov;160(1):51–63. doi: 10.1006/dbio.1993.1285. [DOI] [PubMed] [Google Scholar]
- Heberlein U., Moses K. Mechanisms of Drosophila retinal morphogenesis: the virtues of being progressive. Cell. 1995 Jun 30;81(7):987–990. doi: 10.1016/s0092-8674(05)80003-0. [DOI] [PubMed] [Google Scholar]
- Heberlein U., Rubin G. M. Star is required in a subset of photoreceptor cells in the developing Drosophila retina and displays dosage sensitive interactions with rough. Dev Biol. 1991 Apr;144(2):353–361. doi: 10.1016/0012-1606(91)90427-5. [DOI] [PubMed] [Google Scholar]
- Hiromi Y., Mlodzik M., West S. R., Rubin G. M., Goodman C. S. Ectopic expression of seven-up causes cell fate changes during ommatidial assembly. Development. 1993 Aug;118(4):1123–1135. doi: 10.1242/dev.118.4.1123. [DOI] [PubMed] [Google Scholar]
- Hoover K. K., Gerasimova T. I., Chien A. J., Corces V. G. Dominant effects of suppressor of Hairy-wing mutations on gypsy-induced alleles of forked and cut in Drosophila melanogaster. Genetics. 1992 Nov;132(3):691–697. doi: 10.1093/genetics/132.3.691. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hortsch M., Bieber A. J., Patel N. H., Goodman C. S. Differential splicing generates a nervous system-specific form of Drosophila neuroglian. Neuron. 1990 May;4(5):697–709. doi: 10.1016/0896-6273(90)90196-m. [DOI] [PubMed] [Google Scholar]
- Ingham P. W., Pinchin S. M., Howard K. R., Ish-Horowicz D. Genetic Analysis of the Hairy Locus in DROSOPHILA MELANOGASTER. Genetics. 1985 Nov;111(3):463–486. doi: 10.1093/genetics/111.3.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kolodkin A. L., Pickup A. T., Lin D. M., Goodman C. S., Banerjee U. Characterization of Star and its interactions with sevenless and EGF receptor during photoreceptor cell development in Drosophila. Development. 1994 Jul;120(7):1731–1745. doi: 10.1242/dev.120.7.1731. [DOI] [PubMed] [Google Scholar]
- Kramer S., West S. R., Hiromi Y. Cell fate control in the Drosophila retina by the orphan receptor seven-up: its role in the decisions mediated by the ras signaling pathway. Development. 1995 May;121(5):1361–1372. doi: 10.1242/dev.121.5.1361. [DOI] [PubMed] [Google Scholar]
- Krauss S., Concordet J. P., Ingham P. W. A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell. 1993 Dec 31;75(7):1431–1444. doi: 10.1016/0092-8674(93)90628-4. [DOI] [PubMed] [Google Scholar]
- Laski F. A., Rio D. C., Rubin G. M. Tissue specificity of Drosophila P element transposition is regulated at the level of mRNA splicing. Cell. 1986 Jan 17;44(1):7–19. doi: 10.1016/0092-8674(86)90480-0. [DOI] [PubMed] [Google Scholar]
- Laufer E., Nelson C. E., Johnson R. L., Morgan B. A., Tabin C. Sonic hedgehog and Fgf-4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud. Cell. 1994 Dec 16;79(6):993–1003. doi: 10.1016/0092-8674(94)90030-2. [DOI] [PubMed] [Google Scholar]
- Lee J. J., Ekker S. C., von Kessler D. P., Porter J. A., Sun B. I., Beachy P. A. Autoproteolysis in hedgehog protein biogenesis. Science. 1994 Dec 2;266(5190):1528–1537. doi: 10.1126/science.7985023. [DOI] [PubMed] [Google Scholar]
- Lee J. J., von Kessler D. P., Parks S., Beachy P. A. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell. 1992 Oct 2;71(1):33–50. doi: 10.1016/0092-8674(92)90264-d. [DOI] [PubMed] [Google Scholar]
- Ma C., Moses K. Wingless and patched are negative regulators of the morphogenetic furrow and can affect tissue polarity in the developing Drosophila compound eye. Development. 1995 Aug;121(8):2279–2289. doi: 10.1242/dev.121.8.2279. [DOI] [PubMed] [Google Scholar]
- Ma C., Zhou Y., Beachy P. A., Moses K. The segment polarity gene hedgehog is required for progression of the morphogenetic furrow in the developing Drosophila eye. Cell. 1993 Dec 3;75(5):927–938. doi: 10.1016/0092-8674(93)90536-y. [DOI] [PubMed] [Google Scholar]
- Maden M. Developmental biology. The limb bud--Part two. Nature. 1994 Oct 13;371(6498):560–561. doi: 10.1038/371560a0. [DOI] [PubMed] [Google Scholar]
- Mardon G., Solomon N. M., Rubin G. M. dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila. Development. 1994 Dec;120(12):3473–3486. doi: 10.1242/dev.120.12.3473. [DOI] [PubMed] [Google Scholar]
- Mohler J. Requirements for hedgehog, a segmental polarity gene, in patterning larval and adult cuticle of Drosophila. Genetics. 1988 Dec;120(4):1061–1072. doi: 10.1093/genetics/120.4.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mohler J., Vani K. Molecular organization and embryonic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila. Development. 1992 Aug;115(4):957–971. doi: 10.1242/dev.115.4.957. [DOI] [PubMed] [Google Scholar]
- Moses K., Rubin G. M. Glass encodes a site-specific DNA-binding protein that is regulated in response to positional signals in the developing Drosophila eye. Genes Dev. 1991 Apr;5(4):583–593. doi: 10.1101/gad.5.4.583. [DOI] [PubMed] [Google Scholar]
- Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
- Niswander L., Jeffrey S., Martin G. R., Tickle C. A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature. 1994 Oct 13;371(6498):609–612. doi: 10.1038/371609a0. [DOI] [PubMed] [Google Scholar]
- O'Kane C. J., Gehring W. J. Detection in situ of genomic regulatory elements in Drosophila. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9123–9127. doi: 10.1073/pnas.84.24.9123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Neill E. M., Ellis M. C., Rubin G. M., Tjian R. Functional domain analysis of glass, a zinc-finger-containing transcription factor in Drosophila. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6557–6561. doi: 10.1073/pnas.92.14.6557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Panganiban G. E., Rashka K. E., Neitzel M. D., Hoffmann F. M. Biochemical characterization of the Drosophila dpp protein, a member of the transforming growth factor beta family of growth factors. Mol Cell Biol. 1990 Jun;10(6):2669–2677. doi: 10.1128/mcb.10.6.2669. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Porter J. A., von Kessler D. P., Ekker S. C., Young K. E., Lee J. J., Moses K., Beachy P. A. The product of hedgehog autoproteolytic cleavage active in local and long-range signalling. Nature. 1995 Mar 23;374(6520):363–366. doi: 10.1038/374363a0. [DOI] [PubMed] [Google Scholar]
- Quiring R., Walldorf U., Kloter U., Gehring W. J. Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. Science. 1994 Aug 5;265(5173):785–789. doi: 10.1126/science.7914031. [DOI] [PubMed] [Google Scholar]
- Ready D. F., Hanson T. E., Benzer S. Development of the Drosophila retina, a neurocrystalline lattice. Dev Biol. 1976 Oct 15;53(2):217–240. doi: 10.1016/0012-1606(76)90225-6. [DOI] [PubMed] [Google Scholar]
- Robertson H. M., Preston C. R., Phillis R. W., Johnson-Schlitz D. M., Benz W. K., Engels W. R. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics. 1988 Mar;118(3):461–470. doi: 10.1093/genetics/118.3.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spencer F. A., Hoffmann F. M., Gelbart W. M. Decapentaplegic: a gene complex affecting morphogenesis in Drosophila melanogaster. Cell. 1982 Mar;28(3):451–461. doi: 10.1016/0092-8674(82)90199-4. [DOI] [PubMed] [Google Scholar]
- Tabata T., Eaton S., Kornberg T. B. The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation. Genes Dev. 1992 Dec;6(12B):2635–2645. doi: 10.1101/gad.6.12b.2635. [DOI] [PubMed] [Google Scholar]
- Thaker H. M., Kankel D. R. Mosaic analysis gives an estimate of the extent of genomic involvement in the development of the visual system in Drosophila melanogaster. Genetics. 1992 Aug;131(4):883–894. doi: 10.1093/genetics/131.4.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomlinson A., Ready D. F. Cell fate in the Drosophila ommatidium. Dev Biol. 1987 Sep;123(1):264–275. doi: 10.1016/0012-1606(87)90448-9. [DOI] [PubMed] [Google Scholar]
- Wemmer T., Klämbt C. A genetic analysis of the Drosophila closely linked interacting genes bulge, argos and soba. Genetics. 1995 Jun;140(2):629–641. doi: 10.1093/genetics/140.2.629. [DOI] [PMC free article] [PubMed] [Google Scholar]