Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1993 Jun;12(6):2411–2418. doi: 10.1002/j.1460-2075.1993.tb05895.x

The Drosophila neuralized gene encodes a C3HC4 zinc finger.

B D Price 1, Z Chang 1, R Smith 1, S Bockheim 1, A Laughon 1
PMCID: PMC413475  PMID: 8508767

Abstract

The neurogenic genes of Drosophila are required for cell-cell communication that determines the choice between neuronal and epidermal cell fate. Here we report the molecular characterization of the neurogenic gene neuralized (neu) and show that it encodes a protein containing a C3HC4 zinc finger DNA-binding motif. This motif has been previously characterized in a variety of regulatory proteins, including transcription factors, locus-specific Drosophila chromosomal proteins, and oncoproteins. These results suggest a nuclear function for neu in the cell-cell signalling process responsible for inhibiting neuronal determination.

Full text

PDF
2411

Images in this article

2412Image
on p.2412
2412Image
on p.2412
2415Image
on p.2415
2417Image
on p.2417

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Artavanis-Tsakonas S., Simpson P. Choosing a cell fate: a view from the Notch locus. Trends Genet. 1991 Nov-Dec;7(11-12):403–408. doi: 10.1016/0168-9525(91)90264-q. [DOI] [PubMed] [Google Scholar]
  2. Austin J., Kimble J. Transcript analysis of glp-1 and lin-12, homologous genes required for cell interactions during development of C. elegans. Cell. 1989 Aug 11;58(3):565–571. doi: 10.1016/0092-8674(89)90437-6. [DOI] [PubMed] [Google Scholar]
  3. Bier E., Vaessin H., Shepherd S., Lee K., McCall K., Barbel S., Ackerman L., Carretto R., Uemura T., Grell E. Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector. Genes Dev. 1989 Sep;3(9):1273–1287. doi: 10.1101/gad.3.9.1273. [DOI] [PubMed] [Google Scholar]
  4. Blake T. J., Shapiro M., Morse H. C., 3rd, Langdon W. Y. The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif. Oncogene. 1991 Apr;6(4):653–657. [PubMed] [Google Scholar]
  5. Boulianne G. L., de la Concha A., Campos-Ortega J. A., Jan L. Y., Jan Y. N. The Drosophila neurogenic gene neuralized encodes a novel protein and is expressed in precursors of larval and adult neurons. EMBO J. 1991 Oct;10(10):2975–2983. doi: 10.1002/j.1460-2075.1991.tb07848.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  7. Brunk B. P., Martin E. C., Adler P. N. Drosophila genes Posterior Sex Combs and Suppressor two of zeste encode proteins with homology to the murine bmi-1 oncogene. Nature. 1991 Sep 26;353(6342):351–353. doi: 10.1038/353351a0. [DOI] [PubMed] [Google Scholar]
  8. Campos-Ortega J. A., Jan Y. N. Genetic and molecular bases of neurogenesis in Drosophila melanogaster. Annu Rev Neurosci. 1991;14:399–420. doi: 10.1146/annurev.ne.14.030191.002151. [DOI] [PubMed] [Google Scholar]
  9. Cheung A. K. Cloning of the latency gene and the early protein 0 gene of pseudorabies virus. J Virol. 1991 Oct;65(10):5260–5271. doi: 10.1128/jvi.65.10.5260-5271.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  11. Coffman C., Harris W., Kintner C. Xotch, the Xenopus homolog of Drosophila notch. Science. 1990 Sep 21;249(4975):1438–1441. doi: 10.1126/science.2402639. [DOI] [PubMed] [Google Scholar]
  12. Corbin V., Michelson A. M., Abmayr S. M., Neel V., Alcamo E., Maniatis T., Young M. W. A role for the Drosophila neurogenic genes in mesoderm differentiation. Cell. 1991 Oct 18;67(2):311–323. doi: 10.1016/0092-8674(91)90183-y. [DOI] [PubMed] [Google Scholar]
  13. Dang C. V., Lee W. M. Nuclear and nucleolar targeting sequences of c-erb-A, c-myb, N-myc, p53, HSP70, and HIV tat proteins. J Biol Chem. 1989 Oct 25;264(30):18019–18023. [PubMed] [Google Scholar]
  14. Ellisen L. W., Bird J., West D. C., Soreng A. L., Reynolds T. C., Smith S. D., Sklar J. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991 Aug 23;66(4):649–661. doi: 10.1016/0092-8674(91)90111-b. [DOI] [PubMed] [Google Scholar]
  15. Everett R. D. Trans activation of transcription by herpes virus products: requirement for two HSV-1 immediate-early polypeptides for maximum activity. EMBO J. 1984 Dec 20;3(13):3135–3141. doi: 10.1002/j.1460-2075.1984.tb02270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fehon R. G., Kooh P. J., Rebay I., Regan C. L., Xu T., Muskavitch M. A., Artavanis-Tsakonas S. Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila. Cell. 1990 May 4;61(3):523–534. doi: 10.1016/0092-8674(90)90534-l. [DOI] [PubMed] [Google Scholar]
  17. Freemont P. S., Hanson I. M., Trowsdale J. A novel cysteine-rich sequence motif. Cell. 1991 Feb 8;64(3):483–484. doi: 10.1016/0092-8674(91)90229-r. [DOI] [PubMed] [Google Scholar]
  18. Frigerio G., Burri M., Bopp D., Baumgartner S., Noll M. Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network. Cell. 1986 Dec 5;47(5):735–746. doi: 10.1016/0092-8674(86)90516-7. [DOI] [PubMed] [Google Scholar]
  19. Gelman I. H., Silverstein S. Identification of immediate early genes from herpes simplex virus that transactivate the virus thymidine kinase gene. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5265–5269. doi: 10.1073/pnas.82.16.5265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Greenwald I. lin-12, a nematode homeotic gene, is homologous to a set of mammalian proteins that includes epidermal growth factor. Cell. 1985 Dec;43(3 Pt 2):583–590. doi: 10.1016/0092-8674(85)90230-2. [DOI] [PubMed] [Google Scholar]
  21. Haupt Y., Alexander W. S., Barri G., Klinken S. P., Adams J. M. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Cell. 1991 May 31;65(5):753–763. doi: 10.1016/0092-8674(91)90383-a. [DOI] [PubMed] [Google Scholar]
  22. Heitzler P., Simpson P. The choice of cell fate in the epidermis of Drosophila. Cell. 1991 Mar 22;64(6):1083–1092. doi: 10.1016/0092-8674(91)90263-x. [DOI] [PubMed] [Google Scholar]
  23. Hoppe P. E., Greenspan R. J. Local function of the Notch gene for embryonic ectodermal pathway choice in Drosophila. Cell. 1986 Aug 29;46(5):773–783. doi: 10.1016/0092-8674(86)90353-3. [DOI] [PubMed] [Google Scholar]
  24. Hoppe P. E., Greenspan R. J. The Notch locus of Drosophila is required in epidermal cells for epidermal development. Development. 1990 Aug;109(4):875–885. doi: 10.1242/dev.109.4.875. [DOI] [PubMed] [Google Scholar]
  25. Huang F., Dambly-Chaudière C., Ghysen A. The emergence of sense organs in the wing disc of Drosophila. Development. 1991 Apr;111(4):1087–1095. doi: 10.1242/dev.111.4.1087. [DOI] [PubMed] [Google Scholar]
  26. Jiang J., Kosman D., Ip Y. T., Levine M. The dorsal morphogen gradient regulates the mesoderm determinant twist in early Drosophila embryos. Genes Dev. 1991 Oct;5(10):1881–1891. doi: 10.1101/gad.5.10.1881. [DOI] [PubMed] [Google Scholar]
  27. Kakizuka A., Miller W. H., Jr, Umesono K., Warrell R. P., Jr, Frankel S. R., Murty V. V., Dmitrovsky E., Evans R. M. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991 Aug 23;66(4):663–674. doi: 10.1016/0092-8674(91)90112-c. [DOI] [PubMed] [Google Scholar]
  28. Kidd S., Kelley M. R., Young M. W. Sequence of the notch locus of Drosophila melanogaster: relationship of the encoded protein to mammalian clotting and growth factors. Mol Cell Biol. 1986 Sep;6(9):3094–3108. doi: 10.1128/mcb.6.9.3094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Klämbt C., Knust E., Tietze K., Campos-Ortega J. A. Closely related transcripts encoded by the neurogenic gene complex enhancer of split of Drosophila melanogaster. EMBO J. 1989 Jan;8(1):203–210. doi: 10.1002/j.1460-2075.1989.tb03365.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Knust E., Schrons H., Grawe F., Campos-Ortega J. A. Seven genes of the Enhancer of split complex of Drosophila melanogaster encode helix-loop-helix proteins. Genetics. 1992 Oct;132(2):505–518. doi: 10.1093/genetics/132.2.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kopczynski C. C., Alton A. K., Fechtel K., Kooh P. J., Muskavitch M. A. Delta, a Drosophila neurogenic gene, is transcriptionally complex and encodes a protein related to blood coagulation factors and epidermal growth factor of vertebrates. Genes Dev. 1988 Dec;2(12B):1723–1735. doi: 10.1101/gad.2.12b.1723. [DOI] [PubMed] [Google Scholar]
  32. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  33. Martin E. C., Adler P. N. The Polycomb group gene Posterior Sex Combs encodes a chromosomal protein. Development. 1993 Feb;117(2):641–655. doi: 10.1242/dev.117.2.641. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. O'Connell P. O., Rosbash M. Sequence, structure, and codon preference of the Drosophila ribosomal protein 49 gene. Nucleic Acids Res. 1984 Jul 11;12(13):5495–5513. doi: 10.1093/nar/12.13.5495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. O'Hare P., Hayward G. S. Evidence for a direct role for both the 175,000- and 110,000-molecular-weight immediate-early proteins of herpes simplex virus in the transactivation of delayed-early promoters. J Virol. 1985 Mar;53(3):751–760. doi: 10.1128/jvi.53.3.751-760.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. O'Hare P., Hayward G. S. Three trans-acting regulatory proteins of herpes simplex virus modulate immediate-early gene expression in a pathway involving positive and negative feedback regulation. J Virol. 1985 Dec;56(3):723–733. doi: 10.1128/jvi.56.3.723-733.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Paro R. Imprinting a determined state into the chromatin of Drosophila. Trends Genet. 1990 Dec;6(12):416–421. doi: 10.1016/0168-9525(90)90303-n. [DOI] [PubMed] [Google Scholar]
  39. Perry L. J., Rixon F. J., Everett R. D., Frame M. C., McGeoch D. J. Characterization of the IE110 gene of herpes simplex virus type 1. J Gen Virol. 1986 Nov;67(Pt 11):2365–2380. doi: 10.1099/0022-1317-67-11-2365. [DOI] [PubMed] [Google Scholar]
  40. Poole S. J., Kauvar L. M., Drees B., Kornberg T. The engrailed locus of Drosophila: structural analysis of an embryonic transcript. Cell. 1985 Jan;40(1):37–43. doi: 10.1016/0092-8674(85)90306-x. [DOI] [PubMed] [Google Scholar]
  41. Proudfoot N. J., Brownlee G. G. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. doi: 10.1038/263211a0. [DOI] [PubMed] [Google Scholar]
  42. Quinlan M. P., Knipe D. M. Stimulation of expression of a herpes simplex virus DNA-binding protein by two viral functions. Mol Cell Biol. 1985 May;5(5):957–963. doi: 10.1128/mcb.5.5.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Rao Y., Jan L. Y., Jan Y. N. Similarity of the product of the Drosophila neurogenic gene big brain to transmembrane channel proteins. Nature. 1990 May 10;345(6271):163–167. doi: 10.1038/345163a0. [DOI] [PubMed] [Google Scholar]
  44. Rastelli L., Chan C. S., Pirrotta V. Related chromosome binding sites for zeste, suppressors of zeste and Polycomb group proteins in Drosophila and their dependence on Enhancer of zeste function. EMBO J. 1993 Apr;12(4):1513–1522. doi: 10.1002/j.1460-2075.1993.tb05795.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Reddy B. A., Etkin L. D. A unique bipartite cysteine-histidine motif defines a subfamily of potential zinc-finger proteins. Nucleic Acids Res. 1991 Nov 25;19(22):6330–6330. doi: 10.1093/nar/19.22.6330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Reddy B. A., Kloc M., Etkin L. The cloning and characterization of a maternally expressed novel zinc finger nuclear phosphoprotein (xnf7) in Xenopus laevis. Dev Biol. 1991 Nov;148(1):107–116. doi: 10.1016/0012-1606(91)90321-s. [DOI] [PubMed] [Google Scholar]
  47. Ruohola H., Bremer K. A., Baker D., Swedlow J. R., Jan L. Y., Jan Y. N. Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila. Cell. 1991 Aug 9;66(3):433–449. doi: 10.1016/0092-8674(81)90008-8. [DOI] [PubMed] [Google Scholar]
  48. Salvato M. S., Shimomaye E. M. The completed sequence of lymphocytic choriomeningitis virus reveals a unique RNA structure and a gene for a zinc finger protein. Virology. 1989 Nov;173(1):1–10. doi: 10.1016/0042-6822(89)90216-x. [DOI] [PubMed] [Google Scholar]
  49. Sasai Y., Kageyama R., Tagawa Y., Shigemoto R., Nakanishi S. Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. Genes Dev. 1992 Dec;6(12B):2620–2634. doi: 10.1101/gad.6.12b.2620. [DOI] [PubMed] [Google Scholar]
  50. Skeath J. B., Carroll S. B. Regulation of proneural gene expression and cell fate during neuroblast segregation in the Drosophila embryo. Development. 1992 Apr;114(4):939–946. doi: 10.1242/dev.114.4.939. [DOI] [PubMed] [Google Scholar]
  51. Smoller D., Friedel C., Schmid A., Bettler D., Lam L., Yedvobnick B. The Drosophila neurogenic locus mastermind encodes a nuclear protein unusually rich in amino acid homopolymers. Genes Dev. 1990 Oct;4(10):1688–1700. doi: 10.1101/gad.4.10.1688. [DOI] [PubMed] [Google Scholar]
  52. Tagawa M., Sakamoto T., Shigemoto K., Matsubara H., Tamura Y., Ito T., Nakamura I., Okitsu A., Imai K., Taniguchi M. Expression of novel DNA-binding protein with zinc finger structure in various tumor cells. J Biol Chem. 1990 Nov 15;265(32):20021–20026. [PubMed] [Google Scholar]
  53. Takahashi M., Inaguma Y., Hiai H., Hirose F. Developmentally regulated expression of a human "finger"-containing gene encoded by the 5' half of the ret transforming gene. Mol Cell Biol. 1988 Apr;8(4):1853–1856. doi: 10.1128/mcb.8.4.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Tautz D., Pfeifle C. A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback. Chromosoma. 1989 Aug;98(2):81–85. doi: 10.1007/BF00291041. [DOI] [PubMed] [Google Scholar]
  55. Vässin H., Bremer K. A., Knust E., Campos-Ortega J. A. The neurogenic gene Delta of Drosophila melanogaster is expressed in neurogenic territories and encodes a putative transmembrane protein with EGF-like repeats. EMBO J. 1987 Nov;6(11):3431–3440. doi: 10.1002/j.1460-2075.1987.tb02666.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Weinmaster G., Roberts V. J., Lemke G. A homolog of Drosophila Notch expressed during mammalian development. Development. 1991 Sep;113(1):199–205. doi: 10.1242/dev.113.1.199. [DOI] [PubMed] [Google Scholar]
  57. Wharton K. A., Johansen K. M., Xu T., Artavanis-Tsakonas S. Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell. 1985 Dec;43(3 Pt 2):567–581. doi: 10.1016/0092-8674(85)90229-6. [DOI] [PubMed] [Google Scholar]
  58. Wu C. T., Jones R. S., Lasko P. F., Gelbart W. M. Homeosis and the interaction of zeste and white in Drosophila. Mol Gen Genet. 1989 Sep;218(3):559–564. doi: 10.1007/BF00332424. [DOI] [PubMed] [Google Scholar]
  59. Xu T., Caron L. A., Fehon R. G., Artavanis-Tsakonas S. The involvement of the Notch locus in Drosophila oogenesis. Development. 1992 Aug;115(4):913–922. doi: 10.1242/dev.115.4.913. [DOI] [PubMed] [Google Scholar]
  60. Yochem J., Greenwald I. glp-1 and lin-12, genes implicated in distinct cell-cell interactions in C. elegans, encode similar transmembrane proteins. Cell. 1989 Aug 11;58(3):553–563. doi: 10.1016/0092-8674(89)90436-4. [DOI] [PubMed] [Google Scholar]
  61. Zink B., Paro R. In vivo binding pattern of a trans-regulator of homoeotic genes in Drosophila melanogaster. Nature. 1989 Feb 2;337(6206):468–471. doi: 10.1038/337468a0. [DOI] [PubMed] [Google Scholar]
  62. de Thé H., Lavau C., Marchio A., Chomienne C., Degos L., Dejean A. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell. 1991 Aug 23;66(4):675–684. doi: 10.1016/0092-8674(91)90113-d. [DOI] [PubMed] [Google Scholar]
  63. van Lohuizen M., Frasch M., Wientjens E., Berns A. Sequence similarity between the mammalian bmi-1 proto-oncogene and the Drosophila regulatory genes Psc and Su(z)2. Nature. 1991 Sep 26;353(6342):353–355. doi: 10.1038/353353a0. [DOI] [PubMed] [Google Scholar]
  64. van Lohuizen M., Verbeek S., Scheijen B., Wientjens E., van der Gulden H., Berns A. Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell. 1991 May 31;65(5):737–752. doi: 10.1016/0092-8674(91)90382-9. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES