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 Sxl between two alternative stable expression states.

The primary signal for Drosophila sex determination is the number of X chromosomes relative to the number of sets of autosomes. The present report shows that the numerator of this X/A signal appears to be determined by the cumulative dose of a relatively limited number of discrete X-linked genetic elements, two of which are sisterless-a and sisterless-b. This discovery regarding the nature of the sex determination signal grew out of previous studies of both the likely X/A signal target (the feminizing switch gene, Sex-lethal) and two positive regulators of that target gene (sis-a and daughterless). Combinations of genetic perturbations in these three genes had been shown to have synergistic effects. A model proposed in part to account for these interactions generated a large variety of strong predictions for sex-specific synergistic interactions that would be diagnostic for X/A numerator elements and could distinguish them from other components of the sex determination system. All these predictions, as well as other predictions for X/A numerator elements, are shown here to be fulfilled. The most compelling observations involve sexually reciprocal viability effects of duplications of wild-type genes: combinations of sis-a+, sis-b+ and/or Sxl+ duplications are lethal to males but rescue females from the otherwise lethal effects of changes in other components of the sex determination machinery. The many interactions described here illustrate an important principle that may seem counter-intuitive: perturbations of the sex determination signal for Drosophila generally will not appear to affect adult sexual phenotype. This principle follows from the fact that Sxl is involved in dosage compensation as well as sex determination, and from important aspects of the nature and timing of Sxl's regulation both by the X/A signal and by Sxl's own products (positive autoregulation). These factors mask potential effects on adult sexual differentiation by causing the premature death of cells and/or individuals. The fact that the vast array of results presented here conform to this principle is strong evidence in favor of a "binary state" model for Sxl regulation by the X/A signal. This model is favored over an alternative "multiple state" hypothesis that was proposed by others in a different study of the X/A signal. In that same study it was concluded that region 3E8-4F11 of the X chromosome contained especially potent X/A numerator elements.(ABSTRACT TRUNCATED AT 400 WORDS)

[1]  T. Cline,et al.  Functional changes associated with structural alterations induced by mobilization of a P element inserted in the Sex-lethal gene of Drosophila. , 1987, Genetics.

[2]  G. Waring,et al.  Cloning and characterization of a dispersed, multicopy, X chromosome sequence in Drosophila melanogaster. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Cline A female-specific lethal lesion in an X-linked positive regulator of the Drosophila sex determination gene, Sex-lethal. , 1986, Genetics.

[4]  T. Cline,et al.  The Sex-lethal gene of drosophila: DNA alterations associated with sex-specific lethal mutations , 1985, Cell.

[5]  T. Kornberg,et al.  The engrailed locus of D. melanogaster provides an essential zygotic function in precellular embryos , 1985, Cell.

[6]  W. Sullivan,et al.  On biological functions mapping to the heterochromatin of Drosophila melanogaster. , 1985, Genetics.

[7]  T. Schüpbach Normal female germ cell differentiation requires the female X chromosome to autosome ratio and expression of sex-lethal in Drosophila melanogaster. , 1985, Genetics.

[8]  Ricardo Villares,et al.  Molecular genetics of the achaete-scute gene complex of D. melanogaster , 1985, Cell.

[9]  T. Cline Autoregulatory functioning of a Drosophila gene product that establish es and maintains the sexually determined state. , 1984, Genetics.

[10]  L. Sánchez,et al.  Sex determination and dosage compensation in Drosophila melanogaster: production of male clones in XX females , 1983, The EMBO journal.

[11]  J. Nicklas,et al.  Vital Genes That Flank Sex-Lethal, an X-Linked Sex-Determining Gene of DROSOPHILA MELANOGASTER. , 1983, Genetics.

[12]  T. Cline The interaction between daughterless and sex-lethal in triploids: a lethal sex-transforming maternal effect linking sex determination and dosage compensation in Drosophila melanogaster. , 1983, Developmental biology.

[13]  A. Garcı́a-Bellido,et al.  Viability of Female Germ-Line Cells Homozygous for Zygotic Lethals in DROSOPHILA MELANOGASTER. , 1983, Genetics.

[14]  T. Cline Maternal and zygotic sex-specific gene interactions in Drosophila melanogaster. , 1980, Genetics.

[15]  T. Cline A male-specific lethal mutation in Drosophila melanogaster that transforms sex. , 1979, Developmental biology.

[16]  S. McKnight,et al.  Post-replicative nonribosomal transcription units in D. melanogaster embryos , 1979, Cell.

[17]  B. Judd,et al.  Analysis of the Cut Locus of DROSOPHILA MELANOGASTER. , 1979, Genetics.

[18]  A. Garcı́a-Bellido,et al.  Genetic Analysis of the Achaete-Scute System of DROSOPHILA MELANOGASTER. , 1979, Genetics.

[19]  T. Cline Two closely linked mutations in Drosophila melanogaster that are lethal to opposite sexes and interact with daughterless. , 1978, Genetics.

[20]  A. Garcı́a-Bellido,et al.  Developmental Analysis of the Achaete-Scute System of DROSOPHILA MELANOGASTER. , 1978, Genetics.

[21]  P. Ripoll,et al.  Behavior of somatic cells homozygous for zygotic lethals in Drosophila melanogaster. , 1977, Genetics.

[22]  T. Cline A sex-specific, temperature-sensitive maternal effect of the daughterless mutation of Drosophila melanogaster. , 1976, Genetics.

[23]  S. McKnight,et al.  Ultrastructural patterns of RNA synthesis during early embryogenesis of Drosophila melanogaster , 1976, Cell.

[24]  P. Bryant,et al.  Mosaic analysis of lethal mutations in Drosophila. , 1973, Genetics.

[25]  S. C. Lakhotia,et al.  Chromosomal basis of dosage compensation in Drosophila. I. Cellular autonomy of hyperactivity of the male X-chromosome in salivary glands and sex differentiation. , 1969, Genetical research.

[26]  C. Tokunaga,et al.  Cell lineage and differentiation on the male foreleg of Drosophila melanogaster. , 1962, Developmental biology.

[27]  C. Bridges Sex in Relation to Chromosomes and Genes , 1925, The American Naturalist.

[28]  C. Bridges TRIPLOID INTERSEXES IN DROSOPHILA MELANOGASTER. , 1921, Science.

[29]  A. Sturtevant Genetic Studies on DROSOPHILA SIMULANS. III. Autosomal Genes. General Discussion. , 1921, Genetics.

[30]  J. Gergen,et al.  Dosage Compensation in Drosophila: Evidence That daughterless and Sex-lethal Control X Chromosome Activity at the Blastoderm Stage of Embryogenesis. , 1987, Genetics.

[31]  T. Cline,et al.  The relationship of relative gene dose to the complex phenotype of the daughterless locus in Drosophila. , 1986, Developmental genetics.

[32]  E. Eicher,et al.  Genetic control of primary sex determination in mice. , 1986, Annual review of genetics.

[33]  T. Cline,et al.  Sex-lethal, a link between sex determination and sexual differentiation in Drosophila melanogaster. , 1985, Cold Spring Harbor symposia on quantitative biology.

[34]  B. S. Baker,et al.  Control of sexual differentiation in Drosophila melanogaster. , 1985, Cold Spring Harbor symposia on quantitative biology.

[35]  B. S. Baker,et al.  Sex determination and dosage compensation in Drosophila melanogaster. , 1983, Annual review of genetics.

[36]  T. Schüpbach,et al.  Autosomal mutations that interfere with sex determination in somatic cells of Drosophila have no direct effect on the germline. , 1982, Developmental biology.

[37]  J. C. Hall,et al.  Fate mapping of nervous system and other internal tissues in genetic mosaics of Drosophila melanogaster. , 1976, Developmental biology.

[38]  A. de la Chapelle,et al.  [Sex determination]. , 1971, Duodecim; laaketieteellinen aikakauskirja.

[39]  D. Lindsley,et al.  Genetic variations of Drosophila melanogaster , 1967 .

[40]  GENETIC STUDIES ON DROSOPHILA SIMULANS , 2022 .