Abstract
Cell proliferation in the excretory organs of Drosophila, the Malpighian tubules (MT), is under the control of a neural tip cell. This unique cell is singled out from equivalent MT primordial cells in response to Notch signalling. We show that the gene Krüppel (Kr), best known for its segmentation function in the early embryo, is under the control of the Notch-dependent signalling process. Lack-of-function and gain-of-function experiments demonstrate that Kr activity determines the neural fate of tip cells by acting as a direct downstream target of proneural basic helix-loop-helix (bHLH) proteins that are restricted in response to Notch signalling. We have identified a unique cis-acting element that mediates all spatial and temporal aspects of Kr gene expression during MT development. This element contains functional binding sites for the restricted proneural bHLH factors and Fork head protein which is expressed in all MT cells. Our results suggest a mechanism in which these transcription factors cooperate to set up a unique cell fate within an equivalence group of cells by restricting the activity of the developmental switch gene Kr in response to Notch signalling.
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Selected References
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- Artavanis-Tsakonas S., Matsuno K., Fortini M. E. Notch signaling. Science. 1995 Apr 14;268(5208):225–232. doi: 10.1126/science.7716513. [DOI] [PubMed] [Google Scholar]
- Brand A. H., Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993 Jun;118(2):401–415. doi: 10.1242/dev.118.2.401. [DOI] [PubMed] [Google Scholar]
- Cabrera C. V., Alonso M. C., Huikeshoven H. Regulation of scute function by extramacrochaete in vitro and in vivo. Development. 1994 Dec;120(12):3595–3603. doi: 10.1242/dev.120.12.3595. [DOI] [PubMed] [Google Scholar]
- Cabrera C. V., Alonso M. C. Transcriptional activation by heterodimers of the achaete-scute and daughterless gene products of Drosophila. EMBO J. 1991 Oct;10(10):2965–2973. doi: 10.1002/j.1460-2075.1991.tb07847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Campuzano S., Modolell J. Patterning of the Drosophila nervous system: the achaete-scute gene complex. Trends Genet. 1992 Jun;8(6):202–208. doi: 10.1016/0168-9525(92)90234-u. [DOI] [PubMed] [Google Scholar]
- Cleaver J. E. It was a very good year for DNA repair. Cell. 1994 Jan 14;76(1):1–4. doi: 10.1016/0092-8674(94)90165-1. [DOI] [PubMed] [Google Scholar]
- Cubas P., Modolell J., Ruiz-Gómez M. The helix-loop-helix extramacrochaetae protein is required for proper specification of many cell types in the Drosophila embryo. Development. 1994 Sep;120(9):2555–2566. doi: 10.1242/dev.120.9.2555. [DOI] [PubMed] [Google Scholar]
- Ellis H. M. Embryonic expression and function of the Drosophila helix-loop-helix gene, extramacrochaetae. Mech Dev. 1994 Jul;47(1):65–72. doi: 10.1016/0925-4773(94)90096-5. [DOI] [PubMed] [Google Scholar]
- Gaul U., Redemann N., Jäckle H. Single amino acid exchanges in the finger domain impair the function of the Drosophila gene Krüppel (Kr). Proc Natl Acad Sci U S A. 1989 Jun;86(12):4599–4603. doi: 10.1073/pnas.86.12.4599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gaul U., Seifert E., Schuh R., Jäckle H. Analysis of Krüppel protein distribution during early Drosophila development reveals posttranscriptional regulation. Cell. 1987 Aug 14;50(4):639–647. doi: 10.1016/0092-8674(87)90037-7. [DOI] [PubMed] [Google Scholar]
- Gaul U., Weigel D. Regulation of Krüppel expression in the anlage of the Malpighian tubules in the Drosophila embryo. Mech Dev. 1990 Dec;33(1):57–67. doi: 10.1016/0925-4773(90)90135-9. [DOI] [PubMed] [Google Scholar]
- Giebel B., Stüttem I., Hinz U., Campos-Ortega J. A. Lethal of scute requires overexpression of daughterless to elicit ectopic neuronal development during embryogenesis in Drosophila. Mech Dev. 1997 Apr;63(1):75–87. doi: 10.1016/s0925-4773(97)00029-4. [DOI] [PubMed] [Google Scholar]
- Grenningloh G., Rehm E. J., Goodman C. S. Genetic analysis of growth cone guidance in Drosophila: fasciclin II functions as a neuronal recognition molecule. Cell. 1991 Oct 4;67(1):45–57. doi: 10.1016/0092-8674(91)90571-f. [DOI] [PubMed] [Google Scholar]
- Harbecke R., Janning W. The segmentation gene Krüppel of Drosophila melanogaster has homeotic properties. Genes Dev. 1989 Jan;3(1):114–122. doi: 10.1101/gad.3.1.114. [DOI] [PubMed] [Google Scholar]
- Hartmann C., Landgraf M., Bate M., Jäckle H. Krüppel target gene knockout participates in the proper innervation of a specific set of Drosophila larval muscles. EMBO J. 1997 Sep 1;16(17):5299–5309. doi: 10.1093/emboj/16.17.5299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoch M., Broadie K., Jäckle H., Skaer H. Sequential fates in a single cell are established by the neurogenic cascade in the Malpighian tubules of Drosophila. Development. 1994 Dec;120(12):3439–3450. doi: 10.1242/dev.120.12.3439. [DOI] [PubMed] [Google Scholar]
- Hoch M., Jäckle H. Transcriptional regulation and spatial patterning in Drosophila. Curr Opin Genet Dev. 1993 Aug;3(4):566–573. doi: 10.1016/0959-437x(93)90092-4. [DOI] [PubMed] [Google Scholar]
- Hoch M., Pankratz M. J. Control of gut development by fork head and cell signaling molecules in Drosophila. Mech Dev. 1996 Aug;58(1-2):3–14. doi: 10.1016/s0925-4773(96)00541-2. [DOI] [PubMed] [Google Scholar]
- Hoch M., Schröder C., Seifert E., Jäckle H. cis-acting control elements for Krüppel expression in the Drosophila embryo. EMBO J. 1990 Aug;9(8):2587–2595. doi: 10.1002/j.1460-2075.1990.tb07440.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoch M., Seifert E., Jäckle H. Gene expression mediated by cis-acting sequences of the Krüppel gene in response to the Drosophila morphogens bicoid and hunchback. EMBO J. 1991 Aug;10(8):2267–2278. doi: 10.1002/j.1460-2075.1991.tb07763.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaufmann E., Hoch M., Jäckle H. The interaction of DNA with the DNA-binding domain encoded by the Drosophila gene fork head. Eur J Biochem. 1994 Jul 15;223(2):329–337. doi: 10.1111/j.1432-1033.1994.tb18998.x. [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]
- 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]
- Pankratz M. J., Hoch M. Control of epithelial morphogenesis by cell signaling and integrin molecules in the Drosophila foregut. Development. 1995 Jun;121(6):1885–1898. doi: 10.1242/dev.121.6.1885. [DOI] [PubMed] [Google Scholar]
- Romani S., Jimenez F., Hoch M., Patel N. H., Taubert H., Jäckle H. Krüppel, a Drosophila segmentation gene, participates in the specification of neurons and glial cells. Mech Dev. 1996 Nov;60(1):95–107. doi: 10.1016/s0925-4773(96)00603-x. [DOI] [PubMed] [Google Scholar]
- 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]
- Schmucker D., Taubert H., Jäckle H. Formation of the Drosophila larval photoreceptor organ and its neuronal differentiation require continuous Krüppel gene activity. Neuron. 1992 Dec;9(6):1025–1039. doi: 10.1016/0896-6273(92)90063-j. [DOI] [PubMed] [Google Scholar]
- Singson A., Leviten M. W., Bang A. G., Hua X. H., Posakony J. W. Direct downstream targets of proneural activators in the imaginal disc include genes involved in lateral inhibitory signaling. Genes Dev. 1994 Sep 1;8(17):2058–2071. doi: 10.1101/gad.8.17.2058. [DOI] [PubMed] [Google Scholar]
- 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]
- Van Doren M., Ellis H. M., Posakony J. W. The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless/achaete-scute protein complexes. Development. 1991 Sep;113(1):245–255. doi: 10.1242/dev.113.1.245. [DOI] [PubMed] [Google Scholar]
- Weigel D., Jäckle H. The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? Cell. 1990 Nov 2;63(3):455–456. doi: 10.1016/0092-8674(90)90439-l. [DOI] [PubMed] [Google Scholar]
- Weigel D., Jürgens G., Küttner F., Seifert E., Jäckle H. The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. Cell. 1989 May 19;57(4):645–658. doi: 10.1016/0092-8674(89)90133-5. [DOI] [PubMed] [Google Scholar]
- Wodarz A., Hinz U., Engelbert M., Knust E. Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell. 1995 Jul 14;82(1):67–76. doi: 10.1016/0092-8674(95)90053-5. [DOI] [PubMed] [Google Scholar]
- Young M. W., Wesley C. S. Diverse roles for the Notch receptor in the development of D. melanogaster. Perspect Dev Neurobiol. 1997;4(4):345–355. [PubMed] [Google Scholar]
- Zipursky S. L., Venkatesh T. R., Teplow D. B., Benzer S. Neuronal development in the Drosophila retina: monoclonal antibodies as molecular probes. Cell. 1984 Jan;36(1):15–26. doi: 10.1016/0092-8674(84)90069-2. [DOI] [PubMed] [Google Scholar]