The (ovarian tumor) otu gene resides at 23.2 on the genetic map of the X chromosome and near 7F1 on the cytological map. This germ line-expressed locus behaves as if it encodes a gene product which is required during certain steps in the transformation of oogonia into functional oocytes. On the basis of their ovarian morphologies 17 ethyl methane sulfonate (EMS)-induced mutants have been distributed among three developmental classes as follows: quiescent (eight), oncogenic (four), and differentiated (five). The otu13 and otu14 alleles interact to yield fertile females, and many other heteroallelic combinations show partial complementation. Since many mutant alleles interact beneficially, the functional product of the otu gene may be a multimer. We conclude, from an analysis of heteroallelic interactions and dosage effects, that the abnormal phenotypes observed are graded consequences of reduced levels of functional gene product and that the minimum concentration required for development increases as oogenesis proceeds.

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.

The chromosomes of the ovarian nurse cells of Drosophila melanogaster fall apart during their cycles of endoreduplication. However, chromosomal synapsis occurs in the pseudonurse cells produced in certain mutant females. The resulting polytene chromosomes undergo developmental changes that are strikingly different from those recorded for the giant chromosomes of the larval salivary gland cells.

A small proportion of ovarian chambers from females homozygous for the otu7 (for ovarian tumor) mutation contain an "oocyte" that in its nuclear morphology resembles a nurse cell. Such transformed oocytes also appear in colchicine-poisoned wild type ovaries. Cytophotometric estimates demonstrate that these oocytes have undergone 3-4 additional DNA replications, but that they lag behind the adjacent nurse cells by an average of 1.3 replication cycles. It follows that, under certain circumstances, the definitive oocyte can switch to the nurse cell developmental pathway and therefore that a mechanism normally exists for preventing the further replication of its DNA. In the case of otu7, oocytes sometimes restart their endocyclic DNA replications and produce paired, polytene, homologous chromosomes.