No abstract

Inactivation of the single X chromosome in the primary spermatocytes of species with heterogametic males is postulated as a basic control mechanism on the chromosomal level that is required for normal spermatogenesis. This view is supported by (a) cytological observations of X-chromosome allocycly in the primary spermatocytes of all male-heterogametic organisms that were adequately examined, (b) autoradiographic evidence of early cessation of transcription by the X chromosome in the mouse and three species of grasshopper, and (c) the male sterility of animals with certain X-chromosome rearrangements that cannot be attributed to misfunction of specific genes. X-chromosome inactivation during spermatogenesis is proposed as the ideal system for studies of genetic control at the chromosomal level.Sex chromosomes provide a striking example of differentiation of the chromosomal complement and inferentially of chromosomal function during evolution. It seems reasonable to suppose that natural selection has resulted in a particular distribution of genes between the sex chromosomes and the autosomes that is related to the role of these genes in the development and expression of sexuality. For example, malefertility genes are found on the Y chromosome (Y) in Drosophila, whereas male-determining genes are found on mammalian Y chromosomes. Furthermore, sexual differentiation might depend on males differing in constitution from females (e.g. dosage) with respect to some genes but not others; Bridges' and Goldschmidt's genic balance theories of sex determination (1,2) (11,12) have shown that early condensation of the X in mouse spermatocytes is correlated with late replication; furthermore, Monesi (13) correlated early condensation with genetic inactivation, using cessation of uridine incorporation as the criterion. Similar autoradiographic studies of several species of grasshopper by Henderson (14) demonstrated that the X chromosome replicates later in S (synthetic phase of the cell cycle) 182

We have used Drosophila male meiosis as a model system for genetic dissection of the cytokinesis mechanism. Drosophila mutants defective in meiotic cytokinesis can be easily identified by their multinucleate spermatids. Moreover, the large size of meiotic spindles allows characterization of mutant phenotypes with exquisite cytological resolution. We have screened a collection of 1955 homozygous mutant male sterile lines for those with multinucleate spermatids, and thereby identified mutations in 19 genes required for cytokinesis. These include 16 novel loci and three genes, diaphanous, four wheel drive, and pebble, already known to be involved in Drosophila cytokinesis. To define the primary defects leading to failure of cytokinesis, we analyzed meiotic divisions in male mutants for each of these 19 genes. Examination of preparations stained for tubulin, anillin, KLP3A, and F-actin revealed discrete defects in the components of the cytokinetic apparatus, suggesting that these genes act at four major points in a stepwise pathway for cytokinesis. Our results also indicated that the central spindle and the contractile ring are interdependent structures that interact throughout cytokinesis. Moreover, our genetic and cytological analyses provide further evidence for a cell type-specific control of Drosophila cytokinesis, suggesting that several genes required for meiotic cytokinesis in males are not required for mitotic cytokinesis.

Drosophila melanogaster is a widely used model organism for genetic dissection of developmental processes. To exploit its full potential for studying the genetic basis of male fertility, we performed a large-scale screen for male-sterile (ms) mutations. From a collection of 12,326 strains carrying ethyl-methanesulfonatetreated, homozygous viable second or third chromosomes, 2216 ms lines were identified, constituting the largest collection of ms mutations described to date for any organism. Over 2000 lines were cytologically characterized and, of these, 81% failed during spermatogenesis while 19% manifested postspermatogenic processes. Of the phenotypic categories used to classify the mutants, the largest groups were those that showed visible defects in meiotic chromosome segregation or cytokinesis and those that failed in sperm individualization. We also identified 62 fertile or subfertile lines that showed high levels of chromosome loss due to abnormal mitotic or meiotic chromosome transmission in the male germ line or due to paternal chromosome loss in the early embryo. We argue that the majority of autosomal genes that function in male fertility in Drosophila are represented by one or more alleles in the ms collection. Given the conservation of molecular mechanisms underlying important cellular processes, analysis of these mutations should provide insight into the genetic networks that control male fertility in Drosophila and other organisms, including humans.

CHROMOSOMESGroups of rearrangements that share common features or names are tabulated wherever feasible rather than being listed as separate entries. Their distinguishing features are represented in columns whose orders approximate that of the categories of information listed in full entries. 807 THE GENOME OF DROSOPHILA MELANOGASTER DEFICIENCIES Del(l): setDp(lrf) Del(X c2 ): seeDp(l;f)R Df-3L K : setDf(3L)K Df(l)0-sc,LVM\ see Df(1)260-1 Df(1)05-22-1 references: Fleming. genetics: Deficient for l( 1 )lAa through l( 1 )lAd. Df(1)1-96 references: Reming, DeSimone, and White, 1989, Mol. Cell Biol. 9:719-25. genetics: Deficient for 1(1)1 Aa through ewg. Df(1)1D1 cytology: Df(l)14D;15C. references: Mason, Green, Shaw, and Boyd, 1981, Mutat. Res. 81: 329-43. genetics: Deficient for M( 1 )14F. Df(1)2/9A cytology: Df( 1 )20B;20C. origin: Induced by MR. references: Eeken, Sobels, Hyland, and Schalet, 1985, Mutat. Res. 150: 261-75. genetics: Deficient for 1(1 )20Bb 7 . Df(1)2/19B cytology: Df(l)19F. origin: Induced by MR. references: Eeken, Sobels, Hyland, and Schalet, 1985, Mutat. Res. 150: 261-75. genetics: Deficient for flil-l(l )19Fg 2 . Df(1)2F1-3A4 cytology: Df(l)2Fl ;3A4. discoverer: Green. references: Perrimon, Engstrom, and Mahowald, 1984, Genetics 108: 559-72. 1985, Genetics 111: 23-41. genetics: Deficient for l(l)2Fb-gt. molecular biology: Breakpoint mapped to the DNA at +73.5 (Xho site) and +75.0 (Hind III site) by Haenlin, Steller, Pirrotta, and Mohier, 1985, Cell 40: 827-37. Df(1)5-13 genetics: Deficient for 1(1)1 Aa through 1(1)1 Ac. *Df(1)7aA: Deficiency (1) 7a from Austin cytology: Df(l)3C3-5;3C7-9; inferred from Mackensen's fig. 15F (1935). origin: Xray induced. references: Mackensen, 1935, J. Heredity 26: 163-74 (fig.). genetics: Deficient for fa and spl but not w or ec; heterozy gous female N. Df(1)10-70d cytology: Df(l)8D3;8D8-9. origin: Induced by mutator gene mw. references: Green and Lefevre, 1972, Mutat. Res. 16: 59-64. genetics: Deficient for Iz. Df(1)10RA cytology: 8-13 band deficiency including 7A. discoverer: Cline. references: Nicklas and Cline, 1980, Genetics 94: s76. genetics: Deficient for Sxl but not cm or ct. Df(1)11-83 cytology: Df(l)2F2;3A6. discoverer: Schalet. Df(1)12-70b cytology: Xh26-Xh33. origin: Induced by mutator gene mu. references: Green and Lefevre, 1972, Mutat. Res. 16: 59-64. Df(1)13-70b cytology: Df(l)lA7;lB4. origin: Induced by mutator gene mu. references: Green and Lefevre, 1972, Mutat. Res. 16: 59-64. Df(1)13C3 cytology: Df(l)20A3;20E-F. origin: X ray induced, references: Schalet and Lefevre, 44: 183-200. genetics: Deficient for wap to su(f). *Df(1)14zA origin: X ray induced. discoverer: Mackensen. references: 1935, J. Heredity 26: 163-74 (fig.). genetics: Deficient for/but not fw or r. Df(1)16-, Df(1)17-, Df(1)18cytology: A series of deficiencies for the proximal-most X-linked genes; breakpoints tabulated below, origin: Neutron induced, discoverer: Munoz. 808 CHROMOSOMES -DEFICIENCIES deficiency cytology genetics Df(1)46-1