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The segmentation gene runt is needed to activate Sex-lethal, a gene that controls sex determination and dosage compensation in Drosophila

Published online by Cambridge University Press:  14 April 2009

Miguel Torres
Affiliation:
Centro de Invesligaciones Biologicas, Velazquez 144, 28006 Madrid, Spain
Lucas Sanchez
Affiliation:
Centro de Invesligaciones Biologicas, Velazquez 144, 28006 Madrid, Spain

Summary

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In Drosophila, sex is determined by the relative number of X chromosomes to autosomal sets (X: A ratio). The amount of products from several X-linked genes, called sisterless elements, is used to indicate to Sex-lethal the relative number of X chromosomes present in the cell. In response to the X: A signal, Sex-lethal is activated in females but remains inactive in males, being responsible for the control of both sex determination and dosage compensation. Here we find that the X-linked segmentation gene runt plays a role in this process. Reduced function of runt results in femalespecific lethality and sexual transformation of XX animals that are heterozygous for Sxl or sis loss-of-function mutations. These interactions are suppressed by SxlMI, a mutation that constitutively expresses female Sex-lethal functions, and occur at the time when the X: A signal determines Sex-lethal activity. Moreover, the presence of a loss-of-function runt mutation masculinizes triploid intersexes. On the other hand, runt duplications cause a reduction in male viability by ectopic activation of Sex-lethal. We conclude that runt is needed for the initial step of Sex-lethal activation, but does not have a major role as an X-counting element.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1992

References

Bachiller, D. & Sánchez, L. (1991). Production of XO clones in XX females of Drosophila. Genetical Research 57, 2328.CrossRefGoogle Scholar
Baker, B. S. (1989). Sex in flies: the splice of life. Nature 340, 521524.CrossRefGoogle ScholarPubMed
Baker, B. S. & Belote, J. M. (1983). Sex determination and dosage compensation in Drosophila melanogaster. Annual Review of Genetics 17, 345393.CrossRefGoogle ScholarPubMed
Bell, L. R.Maine, E. M.Schedl, P. & Cline, T. W. (1988). Sex-lethal, a Drosophila sex determination switch gene, exhibits sex-specific RNA splicing and sequence similar to RNA binding proteins. Cell 55, 10371046.CrossRefGoogle ScholarPubMed
Bell, L. R.Horabin, J. I.Schedl, P. & Cline, T. W. (1991). Positive autoregulation of Sex-lethal by alternative splicing maintains the female determined state in Drosophila. Cell 65, 229239.CrossRefGoogle ScholarPubMed
Benezra, R.Davis, R. L.Lockstone, D.Turner, D. L. & Weintraub, H. (1990). The protein Id: a negative regulator of the helix-loop-helix DNA binding proteins. Cell 61, 4959.CrossRefGoogle Scholar
Bopp, D.Bell, L. R.Cline, T. W. & Schedl, P. (1991). Developmental distribution of female-specific Sex-lethal proteins in Drosophila melanogaster. Genes and Development 5, 403415.CrossRefGoogle ScholarPubMed
Bridges, C. B. (1921). Triploid intersexes in Drosophila melanogaster. Science 54, 252254.CrossRefGoogle ScholarPubMed
Bridges, C. B. (1925). Sex in relation to genes and chromosomes. American Naturalist 59, 127137.CrossRefGoogle Scholar
Campuzano, S.Carramolino, L.Cabrera, C. V.Ruiz-Gomez, M.Villares, R.Boronat, A. & Modolell, J. (1985). Molecular genetics of the achaete—scute gene complex of D. melanogaster. Cell 40, 327338.CrossRefGoogle ScholarPubMed
Cabrera, C. V.Martinez-Arias, A. & Bate, M. (1987). The expression of three members of the achaete—scute complex correlates with neuroblasts segregation in Drosophila. Cell 50, 425433.CrossRefGoogle ScholarPubMed
Caudy, M.Grell, E. H.Dambly-Chaudière, C.Ghysen, A.Jan, L. Y. & Jan, Y. N. (1988). The maternal sex determination gene daughterless has zygotic activity necessary for the formation of peripheral neurons in Drosophila. Genes and Development 2, 843852.CrossRefGoogle ScholarPubMed
Cline, T. W. (1978). Two closely-linked mutations in Drosophila melanogaster that are lethal to opposite sexes and interact with daughterless. Genetics 90, 683698.CrossRefGoogle ScholarPubMed
Cline, T. W. (1983). The interaction between daughterless and Sex-lethal in triploids: a novel-sex transforming maternal effect linking sex determination and dosage compensation in Drosophila melanogaster. Cellularity Biology 95, 260274.Google Scholar
Cline, T. W. (1984). Autoregulatory function of a Drosophila gene product that establishes and maintains the sexually determined state. Genetics 107, 231277.CrossRefGoogle ScholarPubMed
Cline, T. W. (1986). A female specific lethal lesion in an Xlinked positive regulator of the Drosophila sex determination gene Sex-lethal. Genetics 113, 641663.CrossRefGoogle Scholar
Cline, T. W. (1988). Evidence that ‘sisterless-a’ and ‘sisterless-b’ are two of several discrete ‘numerator elements’ of the X;A sex determination signal in Drosophila that switch Sex-lethal between two alternative stable expression states. Genetics 119, 829862.CrossRefGoogle ScholarPubMed
Cronmiller, C. & Cline, T. W. (1986). The relationship of relative gene dosage to the complex phenotype of the daughterless locus in Drosophila. Cellularity Genetics 7, 205221.Google Scholar
Cronmiller, C. & Cline, T. W. (1987). The Drosophila sex determination gene daughterless has different functions in the germ line versus the soma. Cell 48, 479487.CrossRefGoogle ScholarPubMed
Duffy, J. B. & Gergen, J. P. (1991). The Drosophila segmentation gene runt acts as a position-specific numerator element necessary for the uniform expression of the sex-determining gene Sex-lethal. Genes and Development 5, 21762187.CrossRefGoogle ScholarPubMed
Erickson, J. W. & Cline, T. W. (1991). Molecular nature of the Drosophila sex determination signal and its link to neurogenesis. Science 251, 10711074.CrossRefGoogle ScholarPubMed
Gergen, J. P. (1987). Dosage compensation in Drosophila: evidence that daughterless and Sex-lethal control X chromosome activity at the blastoderm stage of embryogenesis. Genetics 117, 477485.CrossRefGoogle ScholarPubMed
Gergen, J. P. & Wieschaus, E. (1986). Dosage requirements for runt in the segmentation of Drosophila embryos. Cell 45, 289299.CrossRefGoogle ScholarPubMed
Gergen, J. P. & Butler, B. A. (1988). Isolation of the Drosophila segmentation gene runt and analysis of its expression during embryogenesis. Genes and Development 2, 11791193.CrossRefGoogle ScholarPubMed
Garcia-Bellido, A. (1979). Genetic analysis of the achaetescute system of Drosophila melanogaster. Genetics 91, 491520.CrossRefGoogle ScholarPubMed
Granadino, B.Campuzano, S. & Sánchez, L. (1990). The Drosophila melanogaster fl(2)d gene is needed for the female-specific splicing of Sex-lethal RNA. EMBO Journal 9, 25972602.CrossRefGoogle ScholarPubMed
Hodgkin, J. (1989). Drosophila sex determination: a cascade of regulating splicing. Cell 56, 905906.CrossRefGoogle ScholarPubMed
Ingham, P. (1988). The molecular genetics of embryonic pattern formation in Drosophila. Nature 335, 2534 (1988).CrossRefGoogle ScholarPubMed
Ingham, P. & Gergen, P. (1988). Interactions between the pair-rule genes runt, hairy, even-skipped and fushi-tarazu and the establishment of periodic pattern in the Drosophila embryo. Development 104 (Suppl.), 5160.CrossRefGoogle Scholar
Inoue, K.Hoshijima, K.Sakamoto, H. & Shimura, Y. (1990). Binding of the Drosophila Sex-lethal gene product to the alternative splice site of transformer primary transcript. Nature 344, 461463.CrossRefGoogle Scholar
Kania, M. A.Bonner, A. S.Duffy, J. B. & Gergen, P. (1990). The Drosophila segmentation gene runt encodes a novei regulatory protein that is also expressed in the developing nervous system. Genes and Development 4, 17011713.CrossRefGoogle Scholar
Lindsley, D. & Zimm, G. (1985). The genome of Drosophila melanogaster. Part 1: Genes A—K. Drosophila Information Service 62.Google Scholar
Lindsley, D. & Zimm, G. (1987). The genome of Drosophila melanogaster. Part 3: Rearrangements. Drosophila Information Service 65.Google Scholar
Lindsley, D. & Zimm, G. (1990). The genome of Drosophila melanogaster. Part 4: Genes L—Z, balancers, transposable elements. Drosophila Information Service 68.Google Scholar
Lucchesi, J. C. & Skripsky, T. (1981). The link between dosage compensation and sex determination in Drosophila melanogaster. Chromosoma 82, 217227.CrossRefGoogle Scholar
Lucchesi, J. C. & Manning, J. E. (1987). Gene dosage compensation in Drosophila melanogaster. Advances in Genetics 24, 371429.CrossRefGoogle ScholarPubMed
Maroni, G. & Plaut, W. (1973). Dosage compensation in Drosophila melanogaster triploids. I. Autoradiographic study. Chromosoma 40, 361377.CrossRefGoogle ScholarPubMed
Murre, C.McCaw, P. S. & Baltimore, D. (1989 a). A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD and myc proteins. Cell 56, 777783.CrossRefGoogle ScholarPubMed
Murre, C.McCaw, P. S.Vassin, H.Caudy, M.Jan, Y. N.Cabrera, C. V.Buskin, J. N.Hauschka, S. D.Lassar, A. B.Weintraub, H. & Baltimore, D. (1989 b). Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58, 537544.CrossRefGoogle ScholarPubMed
Nöthiger, R. & Steinmann-Zwicky, M. (1985). Sex determination in Drosophila. Trends in Genetics 1, 209215.CrossRefGoogle Scholar
Oliver, B.Perrimon, N. & Mahowald, A. P. (1988). Genetic evidence that the sansfille locus is involved in Drosophila sex determination. Genetics 120, 159171.CrossRefGoogle Scholar
Parkhurst, S. M.Bopp, D. & Ish-Horowicz, D. (1990). X: A ratio, the primary sex-determining signal in Drosophila, is transduced by helix—loop—helix proteins. Cell 63, 11791191.CrossRefGoogle Scholar
Perrimon, N.Smouse, D. & Gabor Miklos, G. L. (1989). Developmental Genetics of loci at the base of the X chromosome of Drosophila melanogaster. Genetics 121, 313331.CrossRefGoogle ScholarPubMed
Romani, S.Campuzano, S. & Modolell, J. (1987). The achaete—scute complex is expressed in neurogenic regions of Drosophila embryos. EMBO Journal 6, 20852092.CrossRefGoogle ScholarPubMed
Salz, H. K..Cline, T. W. & Schedl, P. (1987). Functional changes associated with structural alterations induced by mobilization of a P element inserted in the Sex-lethal gene of Drosophila. Genetics 117, 221231.CrossRefGoogle Scholar
Salz, H. K.Maine, E. M.Keyes, L. N.Samuels, M. E.Cline, T. W. & Schedl, P. (1989). The Drosophila femalespecific sex determination gene, Sex-lethal, has a stage-, tissue-, and sex-specific RNAs suggesting multiple modes of regulations. Genes and Development 3, 708719.CrossRefGoogle Scholar
Sánchez, L. & Nöthiger, R. (1983). Sex determination and dosage compensation in Drosophila melanogaster: production of male clones in XX females. EMBO Journal 2, 485491.CrossRefGoogle ScholarPubMed
Sosnowski, B. A.Belote, J. M. & McKeown, M. (1989). Sex-specific alternative splicing of RNA from the transformer gene results from sequence-dependent splice site blockage. Cell 58, 449–59.CrossRefGoogle ScholarPubMed
Steinmann-Zwicky, M. (1988). Sex determination in Drosophila: the X-chromosomal gene liz is required for Sxl activity. EMBO Journal 7, 38893898.CrossRefGoogle ScholarPubMed
Steinmann-Zwicky, M.Amrein, H. & Nöthiger, R. (1990) Genetic control of sex determination in Drosophila. Advances in Genetics 27, 189237.CrossRefGoogle ScholarPubMed
Sun, X. H. & Baltimore, D. (1991). An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in El 2 heterodimers. Cell 64, 459470.CrossRefGoogle ScholarPubMed
Torres, M. & Sánchez, L. (1989). The scute (T4) gene acts as a numerator element of the X: A signal that determines the state of activity of Sex-lethal in Drosophila melanogaster. EMBO Journal 10, 30793086.CrossRefGoogle Scholar
Torres, M. & Sánchez, L. (1991). The sisterless-b function of the Drosophila gene scute is restricted to the stage when the X:A ratio determines the activity of Sex-lethal. Development 113, 715722.CrossRefGoogle Scholar
Villares, R. & Cabrera, C. V. (1987). The achaete—scute gene complex of D. melanogaster: conserved domains in a subset of genes required for neurogenesis and their homology to myc. Cell 50, 415424.CrossRefGoogle Scholar