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. 1991 Nov;129(3):803–823. doi: 10.1093/genetics/129.3.803

Two Genetically and Molecularly Distinct Functions Involved in Early Neurogenesis Reside within the Enhancer of Split Locus of Drosophila Melanogaster

C Delidakis 1, A Preiss 1, D A Hartley 1, S Artavanis-Tsakonas 1
PMCID: PMC1204748  PMID: 1752423

Abstract

Molecular correlation of the genetic aspects of the function of the neurogenic gene Enhancer of split [E(spl)] has previously been hampered by the densely transcribed nature of the chromosomal region within which it resides. We present data indicating that two distinct molecular species contribute to E(spl) function. Analysis of new E(spl) alleles has allowed us to define two complementing functions within the locus. Subsequent phenotypic analysis of different E(spl) deficiencies combined with P element-transformed constructs has demonstrated that these two functions correspond to: (1) a family of helix-loop-helix (HLH) protein-encoding genes and (2) the single copy gene E(spl) m9/10, whose product shares homology with G-protein β subunits. The zygotically active E(spl) HLH genes can, at least partially, substitute for one another's functions and their total copy number determines the activity of the locus. E(spl) m9/10 acts synergistically with the E(spl) HLH genes and other neurogenic genes in the process of neurogenesis. The maternal component of E(spl) m9/10 has the most pronounced effect in neurogenesis, while its zygotic component is predominantly required during postembryonic development. The lethality of trans-heterozygotes of null E(spl) deficiency alleles with a strong Delta point mutation is a result of the concomitant reduction in activity of both E(spl) HLH and m9/10 functions. Immunocytochemical localization of the E(spl) m9/10 protein has revealed that it is a ubiquitously distributed nuclear component in embryonic, larval and imaginal tissues.

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Selected References

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  1. Bjørn S. P., Soltyk A., Beggs J. D., Friesen J. D. PRP4 (RNA4) from Saccharomyces cerevisiae: its gene product is associated with the U4/U6 small nuclear ribonucleoprotein particle. Mol Cell Biol. 1989 Sep;9(9):3698–3709. doi: 10.1128/mcb.9.9.3698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dieckmann C. L., Tzagoloff A. Assembly of the mitochondrial membrane system. CBP6, a yeast nuclear gene necessary for synthesis of cytochrome b. J Biol Chem. 1985 Feb 10;260(3):1513–1520. [PubMed] [Google Scholar]
  3. Doe C. Q., Goodman C. S. Early events in insect neurogenesis. II. The role of cell interactions and cell lineage in the determination of neuronal precursor cells. Dev Biol. 1985 Sep;111(1):206–219. doi: 10.1016/0012-1606(85)90446-4. [DOI] [PubMed] [Google Scholar]
  4. Ellis H. M., Spann D. R., Posakony J. W. extramacrochaetae, a negative regulator of sensory organ development in Drosophila, defines a new class of helix-loop-helix proteins. Cell. 1990 Apr 6;61(1):27–38. doi: 10.1016/0092-8674(90)90212-w. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Garrell J., Modolell J. The Drosophila extramacrochaetae locus, an antagonist of proneural genes that, like these genes, encodes a helix-loop-helix protein. Cell. 1990 Apr 6;61(1):39–48. doi: 10.1016/0092-8674(90)90213-x. [DOI] [PubMed] [Google Scholar]
  7. Ghysen A., Dambly-Chaudière C. From DNA to form: the achaete-scute complex. Genes Dev. 1988 May;2(5):495–501. doi: 10.1101/gad.2.5.495. [DOI] [PubMed] [Google Scholar]
  8. Hart A. C., Krämer H., Van Vactor D. L., Jr, Paidhungat M., Zipursky S. L. Induction of cell fate in the Drosophila retina: the bride of sevenless protein is predicted to contain a large extracellular domain and seven transmembrane segments. Genes Dev. 1990 Nov;4(11):1835–1847. doi: 10.1101/gad.4.11.1835. [DOI] [PubMed] [Google Scholar]
  9. Hartley D. A., Preiss A., Artavanis-Tsakonas S. A deduced gene product from the Drosophila neurogenic locus, enhancer of split, shows homology to mammalian G-protein beta subunit. Cell. 1988 Dec 2;55(5):785–795. doi: 10.1016/0092-8674(88)90134-1. [DOI] [PubMed] [Google Scholar]
  10. Jan L. Y., Jan Y. N. Antibodies to horseradish peroxidase as specific neuronal markers in Drosophila and in grasshopper embryos. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2700–2704. doi: 10.1073/pnas.79.8.2700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jiménez F., Campos-Ortega J. A. Defective neuroblast commitment in mutants of the achaete-scute complex and adjacent genes of D. melanogaster. Neuron. 1990 Jul;5(1):81–89. doi: 10.1016/0896-6273(90)90036-f. [DOI] [PubMed] [Google Scholar]
  12. Johansen K. M., Fehon R. G., Artavanis-Tsakonas S. The notch gene product is a glycoprotein expressed on the cell surface of both epidermal and neuronal precursor cells during Drosophila development. J Cell Biol. 1989 Nov;109(5):2427–2440. doi: 10.1083/jcb.109.5.2427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Karess R. E., Rubin G. M. Analysis of P transposable element functions in Drosophila. Cell. 1984 Aug;38(1):135–146. doi: 10.1016/0092-8674(84)90534-8. [DOI] [PubMed] [Google Scholar]
  14. Kellum R., Schedl P. A position-effect assay for boundaries of higher order chromosomal domains. Cell. 1991 Mar 8;64(5):941–950. doi: 10.1016/0092-8674(91)90318-s. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Knust E., Bremer K. A., Vässin H., Ziemer A., Tepass U., Campos-Ortega J. A. The enhancer of split locus and neurogenesis in Drosophila melanogaster. Dev Biol. 1987 Jul;122(1):262–273. doi: 10.1016/0012-1606(87)90351-4. [DOI] [PubMed] [Google Scholar]
  17. Knust E., Tietze K., Campos-Ortega J. A. Molecular analysis of the neurogenic locus Enhancer of split of Drosophila melanogaster. EMBO J. 1987 Dec 20;6(13):4113–4123. doi: 10.1002/j.1460-2075.1987.tb02757.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Murre C., McCaw P. S., Vaessin H., Caudy M., Jan L. Y., Jan Y. N., Cabrera C. V., Buskin J. N., Hauschka S. D., Lassar A. B. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. doi: 10.1016/0092-8674(89)90434-0. [DOI] [PubMed] [Google Scholar]
  20. Perrimon N., Engstrom L., Mahowald A. P. Zygotic lethals with specific maternal effect phenotypes in Drosophila melanogaster. I. Loci on the X chromosome. Genetics. 1989 Feb;121(2):333–352. doi: 10.1093/genetics/121.2.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Preiss A., Hartley D. A., Artavanis-Tsakonas S. The molecular genetics of Enhancer of split, a gene required for embryonic neural development in Drosophila. EMBO J. 1988 Dec 1;7(12):3917–3927. doi: 10.1002/j.1460-2075.1988.tb03278.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Romani S., Campuzano S., Macagno E. R., Modolell J. Expression of achaete and scute genes in Drosophila imaginal discs and their function in sensory organ development. Genes Dev. 1989 Jul;3(7):997–1007. doi: 10.1101/gad.3.7.997. [DOI] [PubMed] [Google Scholar]
  23. Rubin G. M., Spradling A. C. Genetic transformation of Drosophila with transposable element vectors. Science. 1982 Oct 22;218(4570):348–353. doi: 10.1126/science.6289436. [DOI] [PubMed] [Google Scholar]
  24. Rubin G. M., Spradling A. C. Vectors for P element-mediated gene transfer in Drosophila. Nucleic Acids Res. 1983 Sep 24;11(18):6341–6351. doi: 10.1093/nar/11.18.6341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shepard S. B., Broverman S. A., Muskavitch M. A. A tripartite interaction among alleles of Notch, Delta, and Enhancer of split during imaginal development of Drosophila melanogaster. Genetics. 1989 Jun;122(2):429–438. doi: 10.1093/genetics/122.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Simpson P. Notch and the choice of cell fate in Drosophila neuroepithelium. Trends Genet. 1990 Nov;6(11):343–345. doi: 10.1016/0168-9525(90)90260-d. [DOI] [PubMed] [Google Scholar]
  27. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Vässin H., Vielmetter J., Campos-Ortega J. A. Genetic interactions in early neurogenesis of Drosophila melanogaster. J Neurogenet. 1985 Nov;2(5):291–308. doi: 10.3109/01677068509102325. [DOI] [PubMed] [Google Scholar]
  31. Weintraub H., Davis R., Tapscott S., Thayer M., Krause M., Benezra R., Blackwell T. K., Turner D., Rupp R., Hollenberg S. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 1991 Feb 15;251(4995):761–766. doi: 10.1126/science.1846704. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. de-la-Concha A., Dietrich U., Weigel D., Campos-Ortega J. A. Functional interactions of neurogenic genes of Drosophila melanogaster. Genetics. 1988 Mar;118(3):499–508. doi: 10.1093/genetics/118.3.499. [DOI] [PMC free article] [PubMed] [Google Scholar]

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