Ovarian pathologies generated by various alleles of the otu locus in Drosophila melanogaster

Abstract

A comparative cytological study was made of oogenesis in flies carrying various mutant alleles of the female sterile gene otu. It resides at 22.7 on the genetic map and within subdivision 7F of the cytological map of the X-chromosome. Each of the five ethyl methane sulfonate-induced mutations observed falls into one of three clilsses. In class 1, most mutant ovarioles lack germ cells; in class 2, most mutant ovarioles contain tumorous chambers; and in class 3 mutants, chambers occur that possess defective oocytes. The otu2 allele belongs to class 1; otu' to class 2; and otu3, om4, and otuS to class 3. The mutations have no effects upon female viability or upon the viability and fertility of hemiLygous males. Heterozygous females are fertile and have cytologically normal ovaries. In otu5 homozygotes, all ovarioles contain egg chambers, but oogenesis is prematurely terminated to produce a pseudo-stage 12 oocyte. Ovarioles from otu3 and from vtu4 homozygotes contain both ovarian tumors and oocytes. Pseudonurse cells (PNC), which are cystocytes that have stopped dividing and have entered the nurse cell mode of development, are also abundant. PNCs contain polytene chromosomes. Since the homologs are paired, each nucleus has the haploid number of chromosomes. In chambers lacking an oocyte, the number of PNCs is less than the normal number of nurse cells. In chambers containing an oocyte, the number of accompanying nurse cells may be 15, or above or below normal. In vitellogenic chambers, the chromosomes in the nurse cells connected directly to the oocyte are more expanded than those in more distant nurse cells. The KA14 deficiency lacks the plus allele of otu. KAi4 heterozygotes are fertile and have cytologically normal ovaries. When females carry KA14 and om1, o w , otU4, or otu5,8O% of their ovarioles are agametic. When females carry otu2 and one of the other mutant alleles, the ovarioles proceed further in development. So otu2 produces a product that has a beneficial effect on the test allele. When two different otu alleles are combined in a single fly, the phenotype of the hybrid ovary usually most resembles that of the ovary homozygous for the "stronger"alle1e (the otu mutant that allows oogenesis to proceed farthest). The results indicate that the product of the otu' locus functions at least three different times during oogenesis; first to permit oogonia to proliferate, second to control the division and differentiation of germarial cystocytes, and third to facilitate the normal growth of the ooplasm. The gene product appears to be required in higher concentrations at each developmental period. The lesions produced by the mutations are thought to interfere with the stability or functioning of the gene product, and the ovarian phenotype produced by a given genotype depends upon the concentration of functional gene product available to the germ cells.

A specific ovarian tumor protein isoform is required for efficient differentiation of germ cells in Drosophila oogenesis.

“…It has been proposed that the otu gene product is required in increasing amounts throughout oogenesis and that different classes of otu mutants reflect phenocritical thresholds of functional otu protein expression (King and Riley 1982;King et al 1986). The fact that heteroallehc combinations of some ONC alleles with some DIF alleles yield fertile flies rather than flies with intermediate ovarian pathologies suggests that a second otu product exists and that each complementing allele provides one of the required functions (Storto and King 1987).…”

“…The otu gene is a potentially promising candidate for a molecular analysis of oogenesis, because otu mutants display a remarkable range of ovarian pathologies. Seventeen ethylmethane sulfonate (EMS)-induced, and 13 P-element-induced, or P-element-derived, otu mutants have been recovered (Gans et al 1975;Mohler 1977;Digan 1980;King and Riley 1982;King et al 1986;Mulligan et al 1988;G. Sass and D. Mohler, unpubl.).…”

“…The quiescent (QUI) class is the most severe and represents mutants in which germ cells fail to proliferate, causing ovarioles to appear as empty sheaths of somatic tissue (King and Riley 1982). Mutants from the oncogenic (ONC) class have lost the ability to control cystocyte divisions: the usual four incomplete rounds of mitosis are replaced by complete and continued cell divisions, giving rise to tumorous egg chambers filled with hundreds of undifferentiated cystocytes (King 1979).…”

Molecular localization and developmental expression of the otu locus of Drosophila melanogaster.

“…Homozygous mutant otu females are sterile and display a variety of abnormalities with respect to oocyte and nurse cell development. Heterozygous (otulotu+) females, hemizygous mutant males, and hemizygous wild-type [otu+/Df(otu)] females are fertile (6,21,(23)(24)(25)37). Clonal analysis studies of a mutant allele of this gene, fs(J)116 (otu), showed that the * Corresponding author.…”

The control of sexual identity in theDrosophilagermline

“…1 include that ovo can also behave genetically downstream of otu in some assays (e.g. Hinson and Nagoshi, 1999), and that both ovo and otu are required for germ cell survival in females (King and Riley, 1982;Oliver et al, 1987), unlike Sxl (Schüpbach, 1985), suggesting they have an additional role that is independent of Sxl. There are also other genes thought to act in this process, such as sans fille, a Sxl splicing factor (Salz, 1992), and stand still, which appears to regulate otu expression (Sahut-Barnola and Pauli, 1999).…”