Abstract
Pulses of the steroid hormone ecdysone initiate Drosophila metamorphosis by inducing widespread changes in gene expression. The Broad-Complex (BR-C) and E74 are induced directly by ecdysone and encode families of transcription factors that regulate ecdysone primary- and secondary-response genes. Genetic analyses have revealed that mutations in the BR-C and E74 are lethal during metamorphosis and that these mutations cause some similar lethal phenotypes and alterations in secondary-response gene transcription. To examine whether the BR-C and E74 function together during development, we have combined representative alleles from each BR-C and E74 complementation group. Analysis of the morphological and molecular phenotypes of the double-mutant animals reveals that BR-C and E74 alleles act together to produce both novel and synergistic effects. We find that the BR-C and E74 share functions in puparium formation, pupation and early gene induction. In addition, our evidence suggests that the BR-C and E74 transcription factors may directly interact to regulate the expression of salivary gland glue and late genes. This data is consistent with current models which propose that combinations of ecdysone primary-response genes regulate common morphogenetic pathways during insect metamorphosis.
Full Text
The Full Text of this article is available as a PDF (7.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ashburner M., Chihara C., Meltzer P., Richards G. Temporal control of puffing activity in polytene chromosomes. Cold Spring Harb Symp Quant Biol. 1974;38:655–662. doi: 10.1101/sqb.1974.038.01.070. [DOI] [PubMed] [Google Scholar]
- Beckendorf S. K., Kafatos F. C. Differentiation in the salivary glands of Drosophila melanogaster: characterization of the glue proteins and their developmental appearance. Cell. 1976 Nov;9(3):365–373. doi: 10.1016/0092-8674(76)90081-7. [DOI] [PubMed] [Google Scholar]
- Belyaeva E. S., Aizenzon M. G., Semeshin V. F., Kiss I. I., Koczka K., Baritcheva E. M., Gorelova T. D., Zhimulev I. F. Cytogenetic analysis of the 2B3-4--2B11 region of the X-chromosome of Drosophila melanogaster. I. Cytology of the region and mutant complementation groups. Chromosoma. 1980;81(2):281–306. doi: 10.1007/BF00285954. [DOI] [PubMed] [Google Scholar]
- Boyd L., O'Toole E., Thummel C. S. Patterns of E74A RNA and protein expression at the onset of metamorphosis in Drosophila. Development. 1991 Aug;112(4):981–995. doi: 10.1242/dev.112.4.981. [DOI] [PubMed] [Google Scholar]
- Burtis K. C., Thummel C. S., Jones C. W., Karim F. D., Hogness D. S. The Drosophila 74EF early puff contains E74, a complex ecdysone-inducible gene that encodes two ets-related proteins. Cell. 1990 Apr 6;61(1):85–99. doi: 10.1016/0092-8674(90)90217-3. [DOI] [PubMed] [Google Scholar]
- Crowley T. E., Bond M. W., Meyerowitz E. M. The structural genes for three Drosophila glue proteins reside at a single polytene chromosome puff locus. Mol Cell Biol. 1983 Apr;3(4):623–634. doi: 10.1128/mcb.3.4.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crowley T. E., Meyerowitz E. M. Steroid regulation of RNAs transcribed from the Drosophila 68c polytene chromosome puff. Dev Biol. 1984 Mar;102(1):110–121. doi: 10.1016/0012-1606(84)90179-9. [DOI] [PubMed] [Google Scholar]
- DiBello P. R., Withers D. A., Bayer C. A., Fristrom J. W., Guild G. M. The Drosophila Broad-Complex encodes a family of related proteins containing zinc fingers. Genetics. 1991 Oct;129(2):385–397. doi: 10.1093/genetics/129.2.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Emery I. F., Bedian V., Guild G. M. Differential expression of Broad-Complex transcription factors may forecast tissue-specific developmental fates during Drosophila metamorphosis. Development. 1994 Nov;120(11):3275–3287. doi: 10.1242/dev.120.11.3275. [DOI] [PubMed] [Google Scholar]
- Fletcher J. C., Burtis K. C., Hogness D. S., Thummel C. S. The Drosophila E74 gene is required for metamorphosis and plays a role in the polytene chromosome puffing response to ecdysone. Development. 1995 May;121(5):1455–1465. doi: 10.1242/dev.121.5.1455. [DOI] [PubMed] [Google Scholar]
- Guay P. S., Guild G. M. The ecdysone-induced puffing cascade in Drosophila salivary glands: a Broad-Complex early gene regulates intermolt and late gene transcription. Genetics. 1991 Sep;129(1):169–175. doi: 10.1093/genetics/129.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hansson L., Lambertsson A. Steroid regulation of glue protein genes in Drosophila melanogaster. Hereditas. 1989;110(1):61–67. doi: 10.1111/j.1601-5223.1989.tb00418.x. [DOI] [PubMed] [Google Scholar]
- Huet F., Ruiz C., Richards G. Puffs and PCR: the in vivo dynamics of early gene expression during ecdysone responses in Drosophila. Development. 1993 Jun;118(2):613–627. doi: 10.1242/dev.118.2.613. [DOI] [PubMed] [Google Scholar]
- Kiss I., Beaton A. H., Tardiff J., Fristrom D., Fristrom J. W. Interactions and developmental effects of mutations in the Broad-Complex of Drosophila melanogaster. Genetics. 1988 Feb;118(2):247–259. doi: 10.1093/genetics/118.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kiss I., Bencze G., Fodor G., Szabad J., Fristrom J. W. Prepupal larval mosaics in Drosophila melanogaster. Nature. 1976 Jul 8;262(5564):136–138. doi: 10.1038/262136a0. [DOI] [PubMed] [Google Scholar]
- Korge G. Larval saliva in Drosophila melanogaster: production, composition, and relationship to chromosome puffs. Dev Biol. 1977 Jul 15;58(2):339–355. doi: 10.1016/0012-1606(77)90096-3. [DOI] [PubMed] [Google Scholar]
- Lai Z. C., Rubin G. M. Negative control of photoreceptor development in Drosophila by the product of the yan gene, an ETS domain protein. Cell. 1992 Aug 21;70(4):609–620. doi: 10.1016/0092-8674(92)90430-k. [DOI] [PubMed] [Google Scholar]
- Muskavitch M. A., Hogness D. S. Molecular analysis of a gene in a developmentally regulated puff of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7362–7366. doi: 10.1073/pnas.77.12.7362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Restifo L. L., Guild G. M. An ecdysterone-responsive puff site in Drosophila contains a cluster of seven differentially regulated genes. J Mol Biol. 1986 Apr 20;188(4):517–528. doi: 10.1016/s0022-2836(86)80002-x. [DOI] [PubMed] [Google Scholar]
- Restifo L. L., Guild G. M. Poly(A) shortening of coregulated transcripts in Drosophila. Dev Biol. 1986 Jun;115(2):507–510. doi: 10.1016/0012-1606(86)90271-x. [DOI] [PubMed] [Google Scholar]
- Restifo L. L., White K. Mutations in a steroid hormone-regulated gene disrupt the metamorphosis of the central nervous system in Drosophila. Dev Biol. 1991 Nov;148(1):174–194. doi: 10.1016/0012-1606(91)90328-z. [DOI] [PubMed] [Google Scholar]
- Richards G. The radioimmune assay of ecdysteroid titres in Drosophila melanogaster. Mol Cell Endocrinol. 1981 Mar;21(3):181–197. doi: 10.1016/0303-7207(81)90013-7. [DOI] [PubMed] [Google Scholar]
- Segraves W. A., Hogness D. S. The E75 ecdysone-inducible gene responsible for the 75B early puff in Drosophila encodes two new members of the steroid receptor superfamily. Genes Dev. 1990 Feb;4(2):204–219. doi: 10.1101/gad.4.2.204. [DOI] [PubMed] [Google Scholar]
- Sliter T. J., Gilbert L. I. Developmental arrest and ecdysteroid deficiency resulting from mutations at the dre4 locus of Drosophila. Genetics. 1992 Mar;130(3):555–568. doi: 10.1093/genetics/130.3.555. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Talbot W. S., Swyryd E. A., Hogness D. S. Drosophila tissues with different metamorphic responses to ecdysone express different ecdysone receptor isoforms. Cell. 1993 Jul 2;73(7):1323–1337. doi: 10.1016/0092-8674(93)90359-x. [DOI] [PubMed] [Google Scholar]
- Thomas H. E., Stunnenberg H. G., Stewart A. F. Heterodimerization of the Drosophila ecdysone receptor with retinoid X receptor and ultraspiracle. Nature. 1993 Apr 1;362(6419):471–475. doi: 10.1038/362471a0. [DOI] [PubMed] [Google Scholar]
- Velissariou V., Ashburner M. The secretory proteins of the larval salivary gland of Drosophila melanogaster: Cytogenetic correlation of a protein and a puff. Chromosoma. 1980;77(1):13–27. doi: 10.1007/BF00292038. [DOI] [PubMed] [Google Scholar]
- Yao T. P., Segraves W. A., Oro A. E., McKeown M., Evans R. M. Drosophila ultraspiracle modulates ecdysone receptor function via heterodimer formation. Cell. 1992 Oct 2;71(1):63–72. doi: 10.1016/0092-8674(92)90266-f. [DOI] [PubMed] [Google Scholar]
- von Kalm L., Crossgrove K., Von Seggern D., Guild G. M., Beckendorf S. K. The Broad-Complex directly controls a tissue-specific response to the steroid hormone ecdysone at the onset of Drosophila metamorphosis. EMBO J. 1994 Aug 1;13(15):3505–3516. doi: 10.1002/j.1460-2075.1994.tb06657.x. [DOI] [PMC free article] [PubMed] [Google Scholar]