Abstract
The Drosophila bithorax complex (BX-C) controls segmental development by selectively deploying three protein products, Ubx, abd-A and Abd-B, within specific segments along the body axis. Expression of these products within any one segment (or, more accurately, parasegment) is affected by mutations clustered in a particular region of the BX-C. The regulatory regions defined by this genetic analysis span 20-50 kb and there is one region for each segmental unit. Here we describe regulatory elements from several of these regions, identified by fusion to a Ubx-lacZ gene and analysis in germline transformants. A small DNA fragment from the abx region programs expression with an anterior boundary in the second thoracic segment (parasegment 5). This anterior limit is appropriate, since the abx region normally controls Ubx in parasegment 5. Other regulatory regions of the BX-C that control development of parasegments 6, 7 or 8 contain similar regulatory elements that program expression with anterior limits in parasegments 6, 7 or 8, respectively. These experiments define a class of BX-C regulatory elements that control expression along the anterior-posterior axis. The early appearance of the lacZ patterns in embryos suggests a role for these elements in the initial activation of expression from the BX-C.
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Selected References
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- Akam M. E., Martinez-Arias A. The distribution of Ultrabithorax transcripts in Drosophila embryos. EMBO J. 1985 Jul;4(7):1689–1700. doi: 10.1002/j.1460-2075.1985.tb03838.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beachy P. A., Helfand S. L., Hogness D. S. Segmental distribution of bithorax complex proteins during Drosophila development. Nature. 1985 Feb 14;313(6003):545–551. doi: 10.1038/313545a0. [DOI] [PubMed] [Google Scholar]
- Bellen H. J., O'Kane C. J., Wilson C., Grossniklaus U., Pearson R. K., Gehring W. J. P-element-mediated enhancer detection: a versatile method to study development in Drosophila. Genes Dev. 1989 Sep;3(9):1288–1300. doi: 10.1101/gad.3.9.1288. [DOI] [PubMed] [Google Scholar]
- Bender W., Akam M., Karch F., Beachy P. A., Peifer M., Spierer P., Lewis E. B., Hogness D. S. Molecular Genetics of the Bithorax Complex in Drosophila melanogaster. Science. 1983 Jul 1;221(4605):23–29. doi: 10.1126/science.221.4605.23. [DOI] [PubMed] [Google Scholar]
- Bender W., Weiffenbach B., Karch F., Peifer M. Domains of cis-interaction in the bithorax complex. Cold Spring Harb Symp Quant Biol. 1985;50:173–180. doi: 10.1101/sqb.1985.050.01.023. [DOI] [PubMed] [Google Scholar]
- Bienz M., Saari G., Tremml G., Müller J., Züst B., Lawrence P. A. Differential regulation of Ultrabithorax in two germ layers of Drosophila. Cell. 1988 May 20;53(4):567–576. doi: 10.1016/0092-8674(88)90573-9. [DOI] [PubMed] [Google Scholar]
- Bienz M., Tremml G. Domain of Ultrabithorax expression in Drosophila visceral mesoderm from autoregulation and exclusion. Nature. 1988 Jun 9;333(6173):576–578. doi: 10.1038/333576a0. [DOI] [PubMed] [Google Scholar]
- Boulet A. M., Scott M. P. Control elements of the P2 promoter of the Antennapedia gene. Genes Dev. 1988 Dec;2(12A):1600–1614. doi: 10.1101/gad.2.12a.1600. [DOI] [PubMed] [Google Scholar]
- Brower D. L. Ultrabithorax gene expression in Drosophila imaginal discs and larval nervous system. Development. 1987 Sep;101(1):83–92. doi: 10.1242/dev.101.1.83. [DOI] [PubMed] [Google Scholar]
- Carroll S. B. Zebra patterns in fly embryos: activation of stripes or repression of interstripes? Cell. 1990 Jan 12;60(1):9–16. doi: 10.1016/0092-8674(90)90711-m. [DOI] [PubMed] [Google Scholar]
- Casadaban M. J., Martinez-Arias A., Shapira S. K., Chou J. Beta-galactosidase gene fusions for analyzing gene expression in escherichia coli and yeast. Methods Enzymol. 1983;100:293–308. doi: 10.1016/0076-6879(83)00063-4. [DOI] [PubMed] [Google Scholar]
- Casanova J., Sánchez-Herrero E., Busturia A., Morata G. Double and triple mutant combinations of bithorax complex of Drosophila. EMBO J. 1987 Oct;6(10):3103–3109. doi: 10.1002/j.1460-2075.1987.tb02619.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Celniker S. E., Keelan D. J., Lewis E. B. The molecular genetics of the bithorax complex of Drosophila: characterization of the products of the Abdominal-B domain. Genes Dev. 1989 Sep;3(9):1424–1436. doi: 10.1101/gad.3.9.1424. [DOI] [PubMed] [Google Scholar]
- Driever W., Nüsslein-Volhard C. A gradient of bicoid protein in Drosophila embryos. Cell. 1988 Jul 1;54(1):83–93. doi: 10.1016/0092-8674(88)90182-1. [DOI] [PubMed] [Google Scholar]
- Driever W., Nüsslein-Volhard C. The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo. Nature. 1989 Jan 12;337(6203):138–143. doi: 10.1038/337138a0. [DOI] [PubMed] [Google Scholar]
- Duboule D., Dollé P. The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. EMBO J. 1989 May;8(5):1497–1505. doi: 10.1002/j.1460-2075.1989.tb03534.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duncan I. M. Polycomblike: a gene that appears to be required for the normal expression of the bithorax and antennapedia gene complexes of Drosophila melanogaster. Genetics. 1982 Sep;102(1):49–70. doi: 10.1093/genetics/102.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duncan I. Control of bithorax complex functions by the segmentation gene fushi tarazu of D. melanogaster. Cell. 1986 Oct 24;47(2):297–309. doi: 10.1016/0092-8674(86)90452-6. [DOI] [PubMed] [Google Scholar]
- Ghysen A., O'Kane C. Neural enhancer-like elements as specific cell markers in Drosophila. Development. 1989 Jan;105(1):35–52. doi: 10.1242/dev.105.1.35. [DOI] [PubMed] [Google Scholar]
- Glaser R. L., Wolfner M. F., Lis J. T. Spatial and temporal pattern of hsp26 expression during normal development. EMBO J. 1986 Apr;5(4):747–754. doi: 10.1002/j.1460-2075.1986.tb04277.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goto T., Macdonald P., Maniatis T. Early and late periodic patterns of even skipped expression are controlled by distinct regulatory elements that respond to different spatial cues. Cell. 1989 May 5;57(3):413–422. doi: 10.1016/0092-8674(89)90916-1. [DOI] [PubMed] [Google Scholar]
- Graham A., Papalopulu N., Krumlauf R. The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell. 1989 May 5;57(3):367–378. doi: 10.1016/0092-8674(89)90912-4. [DOI] [PubMed] [Google Scholar]
- Harding K., Hoey T., Warrior R., Levine M. Autoregulatory and gap gene response elements of the even-skipped promoter of Drosophila. EMBO J. 1989 Apr;8(4):1205–1212. doi: 10.1002/j.1460-2075.1989.tb03493.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hiromi Y., Gehring W. J. Regulation and function of the Drosophila segmentation gene fushi tarazu. Cell. 1987 Sep 11;50(6):963–974. doi: 10.1016/0092-8674(87)90523-x. [DOI] [PubMed] [Google Scholar]
- Ingham P. W., Martinez-Arias A. The correct activation of Antennapedia and bithorax complex genes requires the fushi tarazu gene. Nature. 1986 Dec 11;324(6097):592–597. doi: 10.1038/324592a0. [DOI] [PubMed] [Google Scholar]
- Irish V. F., Martinez-Arias A., Akam M. Spatial regulation of the Antennapedia and Ultrabithorax homeotic genes during Drosophila early development. EMBO J. 1989 May;8(5):1527–1537. doi: 10.1002/j.1460-2075.1989.tb03537.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karch F., Bender W., Weiffenbach B. abdA expression in Drosophila embryos. Genes Dev. 1990 Sep;4(9):1573–1587. doi: 10.1101/gad.4.9.1573. [DOI] [PubMed] [Google Scholar]
- Karch F., Weiffenbach B., Peifer M., Bender W., Duncan I., Celniker S., Crosby M., Lewis E. B. The abdominal region of the bithorax complex. Cell. 1985 Nov;43(1):81–96. doi: 10.1016/0092-8674(85)90014-5. [DOI] [PubMed] [Google Scholar]
- 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]
- Kornfeld K., Saint R. B., Beachy P. A., Harte P. J., Peattie D. A., Hogness D. S. Structure and expression of a family of Ultrabithorax mRNAs generated by alternative splicing and polyadenylation in Drosophila. Genes Dev. 1989 Feb;3(2):243–258. doi: 10.1101/gad.3.2.243. [DOI] [PubMed] [Google Scholar]
- Kuziora M. A., McGinnis W. Autoregulation of a Drosophila homeotic selector gene. Cell. 1988 Nov 4;55(3):477–485. doi: 10.1016/0092-8674(88)90034-7. [DOI] [PubMed] [Google Scholar]
- Lewis E. B. A gene complex controlling segmentation in Drosophila. Nature. 1978 Dec 7;276(5688):565–570. doi: 10.1038/276565a0. [DOI] [PubMed] [Google Scholar]
- Lis J. T., Simon J. A., Sutton C. A. New heat shock puffs and beta-galactosidase activity resulting from transformation of Drosophila with an hsp70-lacZ hybrid gene. Cell. 1983 Dec;35(2 Pt 1):403–410. doi: 10.1016/0092-8674(83)90173-3. [DOI] [PubMed] [Google Scholar]
- Macdonald P. M., Struhl G. A molecular gradient in early Drosophila embryos and its role in specifying the body pattern. Nature. 1986 Dec 11;324(6097):537–545. doi: 10.1038/324537a0. [DOI] [PubMed] [Google Scholar]
- Martinez-Arias A., Lawrence P. A. Parasegments and compartments in the Drosophila embryo. Nature. 1985 Feb 21;313(6004):639–642. doi: 10.1038/313639a0. [DOI] [PubMed] [Google Scholar]
- Mitchison T. J., Sedat J. Localization of antigenic determinants in whole Drosophila embryos. Dev Biol. 1983 Sep;99(1):261–264. doi: 10.1016/0012-1606(83)90275-0. [DOI] [PubMed] [Google Scholar]
- Mlodzik M., Gehring W. J. Expression of the caudal gene in the germ line of Drosophila: formation of an RNA and protein gradient during early embryogenesis. Cell. 1987 Feb 13;48(3):465–478. doi: 10.1016/0092-8674(87)90197-8. [DOI] [PubMed] [Google Scholar]
- Mullins M. C., Rio D. C., Rubin G. M. cis-acting DNA sequence requirements for P-element transposition. Genes Dev. 1989 May;3(5):729–738. doi: 10.1101/gad.3.5.729. [DOI] [PubMed] [Google Scholar]
- O'Connor M. B., Binari R., Perkins L. A., Bender W. Alternative RNA products from the Ultrabithorax domain of the bithorax complex. EMBO J. 1988 Feb;7(2):435–445. doi: 10.1002/j.1460-2075.1988.tb02831.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Connor M., Peifer M., Bender W. Construction of large DNA segments in Escherichia coli. Science. 1989 Jun 16;244(4910):1307–1312. doi: 10.1126/science.2660262. [DOI] [PubMed] [Google Scholar]
- Pankratz M. J., Seifert E., Gerwin N., Billi B., Nauber U., Jäckle H. Gradients of Krüppel and knirps gene products direct pair-rule gene stripe patterning in the posterior region of the Drosophila embryo. Cell. 1990 Apr 20;61(2):309–317. doi: 10.1016/0092-8674(90)90811-r. [DOI] [PubMed] [Google Scholar]
- Patel N. H., Martin-Blanco E., Coleman K. G., Poole S. J., Ellis M. C., Kornberg T. B., Goodman C. S. Expression of engrailed proteins in arthropods, annelids, and chordates. Cell. 1989 Sep 8;58(5):955–968. doi: 10.1016/0092-8674(89)90947-1. [DOI] [PubMed] [Google Scholar]
- Peifer M., Bender W. The anterobithorax and bithorax mutations of the bithorax complex. EMBO J. 1986 Sep;5(9):2293–2303. doi: 10.1002/j.1460-2075.1986.tb04497.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Regulski M., Harding K., Kostriken R., Karch F., Levine M., McGinnis W. Homeo box genes of the Antennapedia and bithorax complexes of Drosophila. Cell. 1985 Nov;43(1):71–80. doi: 10.1016/0092-8674(85)90013-3. [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]
- 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]
- Struhl G. A gene product required for correct initiation of segmental determination in Drosophila. Nature. 1981 Sep 3;293(5827):36–41. doi: 10.1038/293036a0. [DOI] [PubMed] [Google Scholar]
- Struhl G., Akam M. Altered distributions of Ultrabithorax transcripts in extra sex combs mutant embryos of Drosophila. EMBO J. 1985 Dec 1;4(12):3259–3264. doi: 10.1002/j.1460-2075.1985.tb04075.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Struhl G., Struhl K., Macdonald P. M. The gradient morphogen bicoid is a concentration-dependent transcriptional activator. Cell. 1989 Jun 30;57(7):1259–1273. doi: 10.1016/0092-8674(89)90062-7. [DOI] [PubMed] [Google Scholar]
- Struhl G., White R. A. Regulation of the Ultrabithorax gene of Drosophila by other bithorax complex genes. Cell. 1985 Dec;43(2 Pt 1):507–519. doi: 10.1016/0092-8674(85)90180-1. [DOI] [PubMed] [Google Scholar]
- Sánchez-Herrero E., Vernós I., Marco R., Morata G. Genetic organization of Drosophila bithorax complex. Nature. 1985 Jan 10;313(5998):108–113. doi: 10.1038/313108a0. [DOI] [PubMed] [Google Scholar]
- Tautz D. Regulation of the Drosophila segmentation gene hunchback by two maternal morphogenetic centres. Nature. 1988 Mar 17;332(6161):281–284. doi: 10.1038/332281a0. [DOI] [PubMed] [Google Scholar]
- Tiong S., Bone L. M., Whittle J. R. Recessive lethal mutations within the bithorax-complex in Drosophila. Mol Gen Genet. 1985;200(2):335–342. doi: 10.1007/BF00425445. [DOI] [PubMed] [Google Scholar]
- Tuggle C. K., Zakany J., Cianetti L., Peschle C., Nguyen-Huu M. C. Region-specific enhancers near two mammalian homeo box genes define adjacent rostrocaudal domains in the central nervous system. Genes Dev. 1990 Feb;4(2):180–189. doi: 10.1101/gad.4.2.180. [DOI] [PubMed] [Google Scholar]
- White R. A., Lehmann R. A gap gene, hunchback, regulates the spatial expression of Ultrabithorax. Cell. 1986 Oct 24;47(2):311–321. doi: 10.1016/0092-8674(86)90453-8. [DOI] [PubMed] [Google Scholar]
- White R. A., Wilcox M. Distribution of Ultrabithorax proteins in Drosophila. EMBO J. 1985 Aug;4(8):2035–2043. doi: 10.1002/j.1460-2075.1985.tb03889.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White R. A., Wilcox M. Protein products of the bithorax complex in Drosophila. Cell. 1984 Nov;39(1):163–171. doi: 10.1016/0092-8674(84)90202-2. [DOI] [PubMed] [Google Scholar]