A New Biological Rhythm Mutant of Drosophila Melanogaster That Identifies a Gene with an Essential Embryonic Function (original) (raw)
Abstract
To identify components of a circadian pacemaker output pathway, we have sought Drosophila mutations that alter the timing of eclosion but do not perturb circadian period or the expression of the activity rhythm. A mutant named lark has been identified, for which daily peaks of eclosion occur abnormally early while populations are synchronized to either light/dark or temperature cycles. The temporal phasing of locomotor activity in lark mutants, however, is entirely normal, as is the free-running period of the circadian pacemaker. The lark strain carries a single P-element insertion which, interestingly, has a dominant effect on the timing of eclosion, but is also associated with a recessive embryonic lethal phenotype. The analysis of excision-generated alleles suggests that the lark gene encodes an essential function. This function is apparently mediated by a transcription unit that is interrupted by the P-induced lark mutation. A combination of in situ hybridization analysis and reporter (β-gal) staining indicates that this transcription unit expresses mRNAs throughout the embryonic central nervous system and in a defined subset of cells in the nervous system of pharate adults. RNAs are first detected at about embryonic stage 11, just prior to the stage at which lethality occurs in lark homozygotes. Based primarily on the observed mutant phenotypes, a function is proposed for the LARK product(s) that is consistent with the pleiotropic nature of lark mutations.
Full Text
The Full Text of this article is available as a PDF (6.9 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abrams J. M., White K., Fessler L. I., Steller H. Programmed cell death during Drosophila embryogenesis. Development. 1993 Jan;117(1):29–43. doi: 10.1242/dev.117.1.29. [DOI] [PubMed] [Google Scholar]
- Ampleford E. J., Steel C. G. Circadian control of a daily rhythm in hemolymph ecdysteroid titer in the insect Rhodnius prolixus (Hemiptera). Gen Comp Endocrinol. 1985 Sep;59(3):453–459. doi: 10.1016/0016-6480(85)90404-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Carlberg C., Bendik I., Wyss A., Meier E., Sturzenbecker L. J., Grippo J. F., Hunziker W. Two nuclear signalling pathways for vitamin D. Nature. 1993 Feb 18;361(6413):657–660. doi: 10.1038/361657a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Dushay M. S., Konopka R. J., Orr D., Greenacre M. L., Kyriacou C. P., Rosbash M., Hall J. C. Phenotypic and genetic analysis of Clock, a new circadian rhythm mutant in Drosophila melanogaster. Genetics. 1990 Jul;125(3):557–578. doi: 10.1093/genetics/125.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ewer J., Frisch B., Hamblen-Coyle M. J., Rosbash M., Hall J. C. Expression of the period clock gene within different cell types in the brain of Drosophila adults and mosaic analysis of these cells' influence on circadian behavioral rhythms. J Neurosci. 1992 Sep;12(9):3321–3349. doi: 10.1523/JNEUROSCI.12-09-03321.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall J. C. Genetics of circadian rhythms. Annu Rev Genet. 1990;24:659–697. doi: 10.1146/annurev.ge.24.120190.003303. [DOI] [PubMed] [Google Scholar]
- Handler A. M., Konopka R. J. Transplantation of a circadian pacemaker in Drosophila. Nature. 1979 May 17;279(5710):236–238. doi: 10.1038/279236a0. [DOI] [PubMed] [Google Scholar]
- Hewes R. S., Truman J. W. The roles of central and peripheral eclosion hormone release in the control of ecdysis behavior in Manduca sexta. J Comp Physiol A. 1991 Jun;168(6):697–707. doi: 10.1007/BF00224359. [DOI] [PubMed] [Google Scholar]
- Horodyski F. M., Riddiford L. M., Truman J. W. Isolation and expression of the eclosion hormone gene from the tobacco hornworm, Manduca sexta. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8123–8127. doi: 10.1073/pnas.86.20.8123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jackson F. R., Newby L. M., Kulkarni S. J. Drosophila GABAergic systems: sequence and expression of glutamic acid decarboxylase. J Neurochem. 1990 Mar;54(3):1068–1078. doi: 10.1111/j.1471-4159.1990.tb02359.x. [DOI] [PubMed] [Google Scholar]
- Konopka R. J., Benzer S. Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2112–2116. doi: 10.1073/pnas.68.9.2112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Konopka R. J., Smith R. F., Orr D. Characterization of Andante, a new Drosophila clock mutant, and its interactions with other clock mutants. J Neurogenet. 1991 Feb;7(2-3):103–114. doi: 10.3109/01677069109066214. [DOI] [PubMed] [Google Scholar]
- 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]
- Morton D. B., Truman J. W. The EGPs: the eclosion hormone and cyclic GMP-regulated phosphoproteins. I. Appearance and partial characterization in the CNS of Manduca sexta. J Neurosci. 1988 Apr;8(4):1326–1337. doi: 10.1523/JNEUROSCI.08-04-01326.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morton D. B., Truman J. W. The EGPs: the eclosion hormone and cyclic GMP-regulated phosphoproteins. II. Regulation of appearance by the steroid hormone 20-hydroxyecdysone in Manduca sexta. J Neurosci. 1988 Apr;8(4):1338–1345. doi: 10.1523/JNEUROSCI.08-04-01338.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newby L. M., Jackson F. R. Drosophila ebony mutants have altered circadian activity rhythms but normal eclosion rhythms. J Neurogenet. 1991 Feb;7(2-3):85–101. doi: 10.3109/01677069109066213. [DOI] [PubMed] [Google Scholar]
- Newby L. M., White L., DiBartolomeis S. M., Walker B. J., Dowse H. B., Ringo J. M., Khuda N., Jackson F. R. Mutational analysis of the Drosophila miniature-dusky (m-dy) locus: effects on cell size and circadian rhythms. Genetics. 1991 Jul;128(3):571–582. doi: 10.1093/genetics/128.3.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oro A. E., McKeown M., Evans R. M. The Drosophila nuclear receptors: new insight into the actions of nuclear receptors in development. Curr Opin Genet Dev. 1992 Apr;2(2):269–274. doi: 10.1016/s0959-437x(05)80284-9. [DOI] [PubMed] [Google Scholar]
- Pittendrigh C. S. Circadian systems. I. The driving oscillation and its assay in Drosophila pseudoobscura. Proc Natl Acad Sci U S A. 1967 Oct;58(4):1762–1767. doi: 10.1073/pnas.58.4.1762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz L. M. Insect muscle as a model for programmed cell death. J Neurobiol. 1992 Nov;23(9):1312–1326. doi: 10.1002/neu.480230918. [DOI] [PubMed] [Google Scholar]
- Shibanaka Y., Hayashi H., Okada N., Fujita N. The crucial role of cyclic GMP in the eclosion hormone mediated signal transduction in the silkworm metamorphoses. Biochem Biophys Res Commun. 1991 Oct 31;180(2):881–886. doi: 10.1016/s0006-291x(05)81147-7. [DOI] [PubMed] [Google Scholar]
- Siwicki K. K., Eastman C., Petersen G., Rosbash M., Hall J. C. Antibodies to the period gene product of Drosophila reveal diverse tissue distribution and rhythmic changes in the visual system. Neuron. 1988 Apr;1(2):141–150. doi: 10.1016/0896-6273(88)90198-5. [DOI] [PubMed] [Google Scholar]
- Sulzman F. M. Microcomputer monitoring of circadian rhythms. Comput Biol Med. 1982;12(4):253–261. doi: 10.1016/0010-4825(82)90030-0. [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]
- Truman J. W., Thorn R. S., Robinow S. Programmed neuronal death in insect development. J Neurobiol. 1992 Nov;23(9):1295–1311. doi: 10.1002/neu.480230917. [DOI] [PubMed] [Google Scholar]
- Vafopoulou X., Steel C. G. Circadian regulation of synthesis of ecdysteroids by prothoracic glands of the insect Rhodnius prolixus: evidence of a dual oscillator system. Gen Comp Endocrinol. 1991 Jul;83(1):27–34. doi: 10.1016/0016-6480(91)90102-c. [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]
- Zerr D. M., Hall J. C., Rosbash M., Siwicki K. K. Circadian fluctuations of period protein immunoreactivity in the CNS and the visual system of Drosophila. J Neurosci. 1990 Aug;10(8):2749–2762. doi: 10.1523/JNEUROSCI.10-08-02749.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zimmerman W. F., Pittendrigh C. S., Pavlidis T. Temperature compensation of the circadian oscillation in drosophila pseudoobscura and its entrainment by temperature cycles. J Insect Physiol. 1968 May;14(5):669–684. doi: 10.1016/0022-1910(68)90226-6. [DOI] [PubMed] [Google Scholar]