Genetics, Vol. 165, 939-943, November 2003, Copyright © 2003

Robert C. King: An Appreciation of His Work

Pamela K. Mulligan1,a
a Ontario, Canada

THE advance of scientific knowledge is a combined product of both the contributions of the individual scientist and the acceptance and authentication of his or her work over time by the larger scientific community. Robert C. King is one of the most distinguished contributors to advancements in genetics, cell biology, and developmental biology. In honor of Bob's seventy-fifth birthday, it seems appropriate to highlight some of his abundant accomplishments.

Among geneticists, Bob King is widely known as a distinguished author and editor of genetics books, but cell and developmental biologists also know him as an accomplished, often ground-breaking researcher. As a researcher, Bob is perhaps most widely recognized for his definitive characterization of the 14 developmental stages of Drosophila oogenesis (see KING 1970 Down), his beloved experimental system. It is largely through his early cytological work that we know about the origin and development of the egg chamber, the basic structural and functional unit of the Drosophila ovary. Briefly, the egg chamber is composed of 16 interconnected germline cells, the cystocytes, 15 of which differentiate as nurse cells and support the growth of the sixteenth cell, the oocyte, through cytoplasmic transfer via intercellular bridges, or ring canals (KING 1970 Down). Such oocyte-nurse cell syncytia are present in a majority of orders of higher insects. In Drosophila (and presumably in other insects possessing polytrophic meroistic ovaries), a cytoskeletal, membranous structure known as the fusome extends through the ring canals during the early stages of oogenesis and is thought to regulate the division patterns and differentiation of the germline cells (reviewed by DE CUEVAS et al. 1997 Down; MCKEARIN 1997 Down). Complex interactions between these cells and the somatic follicle cells that surround them result in the formation of a mature oocyte (reviewed by LASKO 1994 Down).

Bob and co-workers described the formation and early differentiation of the Drosophila egg chamber in the 1960s. Through painstaking three-dimensional (3D) reconstructions of serially sectioned egg chambers, they deciphered the pattern of cystocyte divisions and the formation of the ring canal system (BROWN and KING 1964 Down; KOCH and KING 1966 Down, KOCH and KING 1969 Down; KOCH et al. 1967 Down). During the following two decades, the formation of the fusome was unraveled (KING 1979 Down; KING and STORTO 1988 Down; STORTO and KING 1989 Down). The determination of the spatial relationship between the cells of the egg chamber and their interconnecting organelles was an enormous undertaking involving multiple arduous steps: plastic embedded egg chambers were serially sectioned and photographed at the light and electron microscope levels, composites were made from overlapping micrographs of each section, morphological information from serial composites was meticulously traced by hand on diffusion paper, and information from stacked tracings was then used to construct 3D plastic models of cell clusters.

In electron microscope studies involving painstakingly reconstructed germaria, the regions of germline cyst formation, Bob and colleagues identified the developmental stages in the formation of the 16-cell cluster (KOCH and KING 1966 Down; KOCH et al. 1967 Down). They deduced from their observations that in the anterior region of the germarium reside a small number of single cells, the stem cells. Each of these divides asymmetrically to form two daughter cells, one of which proliferates indefinitely as another stem cell, while the other functions as a cystoblast, which undergoes four synchronous incomplete cytokineses to produce a complex, branched pattern of 16 interconnected cystocytes (KOCH and KING 1966 Down; KOCH et al. 1967 Down).

In a previous ovarian reconstruction study, Bob King had coined the term ring canals to describe the "cytoplasmic pores" that interconnect sister cystocytes (BROWN and KING 1964 Down). Subsequently, he described the formation of the ring canal system at the ultrastructural level in several insect species (CASSIDY and KING 1969 Down; KOCH and KING 1969 Down; KING and AKAI 1971A Down; KINDERMAN and KING 1973 Down). KOCH and KING 1969 Down observed that in D. melanogaster ring canals formed around remnants of mitotic spindles and proposed that interconnected cells arose as a result of incomplete cytokinesis. They also showed that the precise pattern of cystocyte interconnections was linked to the lineage of the cells (KOCH and KING 1969 Down). This study was the first to describe ring canal rim differentiation and to demonstrate that the oocyte was always one of two cells, the pro-oocytes, with four ring canals (KOCH and KING 1969 Down). Diagrams of a sectioned germarium subdivided into morphologically and functionally distinct subregions (KOCH and KING 1966 Down, Figure 1) and of a model showing steps in the formation of the 16-cell cluster (BROWN and KING 1964 Down, Figure 7) are among the most frequently reproduced figures in insect oogenesis-related literature.

The genetic control of Drosophila egg-chamber formation and differentiation is currently the focus of genetic and molecular biological investigations in a number of labs, and Bob's observations have found strong support in recent studies. For example, the existence of germline stem cells and the asymmetric divisions of these cells and their daughters have been confirmed by laser ablation of stem cells (LIN and SPRADLING 1993 Down) and by direct observations using recently identified molecular markers (LIN et al. 1994 Down; LIN and SPRADLING 1995 Down, LIN and SPRADLING 1997 Down; DENG and LIN 1997 Down; DE CUEVAS and SPRADLING 1998 Down). Genetic mutations have been identified that affect stem cell division (LIN and SPRADLING 1997 Down), that abolish the stem cell-to-cystoblast switch (MCKEARIN and OHLSTEIN 1995 Down), and that affect synchrony of cystocyte divisions (DE CUEVAS et al. 1996 Down; DENG and LIN 1997 Down). And two decades after Bob's cytological descriptions (KOCH and KING 1969 Down), the molecular components of ring canals had started to be identified by using genetic and molecular biological approaches (YUE and SPRADLING 1992 Down; XUE and COOLEY 1993 Down). Today the development of a functional ring canal is known to require the sequential assembly of several cytoskeletal proteins in the arrested cleavage furrow, and the directional transport of materials through these organelles is recognized as being integral to the formation of a normal oocyte (ROBINSON and COOLEY 1996 Down).

Bob King's contribution to the field of cell biology deserves special attention. Long before confocal microscopy and staining with multiple fluorescent antibodies, ovaries were stained in Bob's lab with a multitude of vibrantly colored dyes—Schiff reagent, fast green, orange G, azure B bromide, and various combinations of these. At specific concentrations and pHs, these dyes identified the distribution of macromolecules such as proteins, lipids, nucleic acids, or polysaccharides in the developing egg chamber and other tissues (KING et al. 1957 Down; KING 1960 Down; KING and KOCH 1963 Down; BROWN and KING 1964 Down; BUTTERWORTH et al. 1965 Down; CUMMINGS and KING 1969 Down). Many a student was "hooked" on Drosophila research after witnessing the aesthetic beauty of the colorful specimens under the microscope. Instruction in cytology and cytochemistry would follow later in both the lab and the classroom.

Cytochemical investigation was coupled to ultrastructural analysis of cytoplasmic and nuclear components (KING and KOCH 1963 Down; KOCH and KING 1966 Down, KOCH and KING 1969 Down; KING and AKAI 1971A Down, KING and AKAI 1971B Down; JOHNSON and KING 1972 Down, JOHNSON and KING 1974 Down; KING et al. 1978 Down; BISHOP and KING 1984 Down; STORTO and KING 1989 Down). Procedures for fixation, staining, and embedding were developed and perfected for optimum preservation of submicroscopic organelles (e.g., spindle microtubules, synaptonemal complexes, ring canals, and fusomes), and electron micrographs were generated by the thousands with state-of-the art equipment. Through such work, Bob was actually taking part in creating and cultivating new domains in cell and developmental biology. The detailed morphological descriptions of the 14 developmental stages of Drosophila oogenesis (see KING 1970 Down), which are now widely accepted and serve as a foundation for all Drosophila oogenesis-related investigations, are an impressive example of the culmination of such endeavors.

This cytological work was not purely descriptive. What is remarkable about Bob's work is the creative, speculative intelligence with which he interpreted his observations to form hypotheses. Hypotheses were developed to explain why stem-line oogonia are restricted to the anterior region of the ovary, how the branching pattern of the cystocyte cluster arises, or why only one of the two pro-oocytes becomes the oocyte (BROWN and KING 1964 Down; KOCH and KING 1966 Down, l969; KOCH et al. 1967 Down; KING 1975 Down, KING 1979 Down; KING et al. 1982 Down). Furthermore, beginning as early as 1957 (KING and BURNETT 1957 Down; KING et al. 1957 Down), Bob had the foresight to combine his cytological studies with analyses of genetic mutations for a powerful approach to understanding the genetic mechanisms underlying fundamental cellular processes. In doing so, he helped advance the field of developmental genetics. With the precise classification of the developmental stages of oogenesis (see KING 1970 Down) and the isolation of a large number of female-sterile mutations (reviewed by KING and MOHLER 1975 Down; SPRADLING 1993 Down; LASKO 1994 Down), oogenesis in Drosophila is now one of the most thoroughly investigated model developmental systems in which complex cellular functions and interactions are deciphered through the proficient use of genetic mutations and cell and molecular biological techniques.

For insights into the genetic control of oogenesis, Bob studied numerous female sterile mutations. Particularly noteworthy is his work on some mutants belonging to the ovarian tumor class (e.g., otu, fs(1)1621, fu, and fes), in which cystocytes appeared to undergo complete, rather than incomplete, cytokinesis and in which nurse cell and oocyte differentiation were abnormal (KING and BURNETT 1957 Down; KING et al. 1957 Down, KING et al. 1961 Down; KOCH and KING 1964 Down; SMITH and KING 1966 Down; KING 1969 Down; JOHNSON and KING 1972 Down; GOLLIN and KING 1981 Down). His interest in these mutants reflected both his desire to understand the genetic control of germline cytokinesis, as well as his belief that the underlying cause of aberrant germ cell division and differentiation in some ovarian tumor mutants was abnormal fusome formation.

One of the most extensive genetic and cytological characterizations involved the otu gene (KING et al. 1978 Down, KING et al. 1986 Down; KING 1979 Down; DABBS and KING 1980 Down; KING and RILEY 1982 Down; BISHOP and KING 1984 Down; RASCH et al. 1984 Down; STORTO and KING 1987 Down, STORTO and KING 1988 Down, STORTO and KING 1989 Down). Bob and colleagues mapped the otu gene genetically and subdivided the variety of ovarian phenotypes exhibited by otu alleles into three classes on the basis of morphological criteria (KING and RILEY 1982 Down; KING et al. 1986 Down). Careful and systematic analyses of >100 different heterozygous combinations of otu alleles with each other and with a deficiency led Bob to propose that the otu gene product is made early during oogenesis, acts at several subsequent stages, and is required at a higher concentration at each successive developmental period. The concentration of the gene product determines the stage at which oogenesis is disrupted in the mutants (KING and RILEY 1982 Down; KING et al. 1986 Down; STORTO and KING 1987 Down, STORTO and KING 1988 Down; KING and STORTO 1988 Down). His genetic analyses also suggested that otu produces two gene products, which combine to yield fertile flies in some heteroallelic combinations (KING et al. 1986 Down; STORTO and KING 1987 Down, STORTO and KING 1988 Down). These conclusions were later verified by molecular studies, particularly those of Laura Kalfayan and co-workers, who cloned the otu gene and characterized it molecularly (MULLIGAN et al. 1988 Down; STEINHAUER et al. 1989 Down; COMER et al. 1992 Down; STEINHAUER and KALFAYAN 1992 Down; SASS et al. 1993 Down, SASS et al. 1995 Down). In fact, in an article that identified two otu protein isoforms and analyzed their expression patterns, STEINHAUER and KALFAYAN 1992 Down(p. 240) observed, "It is remarkable that the hypothesis developed by King and his colleagues from genetic and morphological analyses should, for the most part, predict observed molecular data so closely."

It was also during the 1970s and 1980s that Bob focused his attention on the formation of the polyfusome (a term he applied to the mature, branched fusome) and made deductions regarding the role of this organelle in the formation of the cystocyte cluster and its differentiation (KING 1979 Down; KING et al. 1982 Down; KING and STORTO 1988 Down; STORTO and KING 1989 Down). Bob's recognition of the developmental significance of the polyfusome epitomizes his exceptional insight and ability to ask pertinent questions, to form hypotheses, and to combine his expertise in genetics and cytology to seek answers to developmental questions.

The fusome had been observed in a variety of insects and was described as cellular material that contained spindle residue and that extended through the ring canals during cystocyte divisions (see TELFER 1975 Down). Bob built on these observations through electron microscope 3D reconstructions and analysis of genetic mutations and proposed that in Drosophila, fusomes serve to arrest cystocyte cytokinesis, synchronize and restrict the number of mitotic divisions, and affect the orientation of the mitotic spindle (KING 1979 Down; KING et al. 1982 Down; STORTO and KING 1989 Down). He also had the insight to suggest that this organelle may function as an oocyte determinant (KING et al. 1982 Down).

In a widely cited article, STORTO and KING 1989 Down used electron microscope 3D reconstructions to analyze fusome structure in wild-type and otu mutant ovaries. They showed that most germ cells in otu ovarian tumors either were single or occurred in clusters of two to three interconnected cells. These cells contained structurally aberrant fusomes, and cystocytes never differentiated into pro-oocytes or nurse cells. These observations supported Bob's belief that an intact polyfusome system was necessary for the production of a branched chain of cystocytes and for their subsequent differentiation. These findings were later confirmed by RODESCH et al. 1997 Down, who showed that fusomes in otu null mutants were aberrant both structurally and in their molecular composition.

While the precise function of the polyfusome still remains to be identified, the quest for this function is now the focus of research by a new generation of scientists. Recent genetic and molecular biological analyses have identified numerous molecular components of the fusome (reviewed by DE CUEVAS et al. 1997 Down; MCKEARIN 1997 Down), and some of Bob's conclusions have been corroborated by immunocytochemical and genetic analyses. For example, his observation that one pole of the spindle lies embedded in the polyfusome during cystocyte divisions has been confirmed by simultaneous staining with microtubule- and fusome-specific antibodies (LIN et al. 1994 Down; LIN and SPRADLING 1995 Down, LIN and SPRADLING 1997 Down; DENG and LIN 1997 Down; MCGRAIL and HAYS 1997 Down; DE CUEVAS and SPRADLING 1998 Down) and his proposal that fusomes synchronize cystocyte divisions is supported by the findings that cells without fusomes divide asynchronously (DE CUEVAS et al. 1996 Down; DENG and LIN 1997 Down) and that various proteins involved in cell cycle regulation associate with the fusome (reviewed by DE CUEVAS et al. 1997 Down). His suggestion that "nonrandom distribution" of fusomal material is related to oocyte determination has found partial support in direct observations of fusome asymmetry during cystoblast and cystocyte divisions (LIN et al. 1994 Down; LIN and SPRADLING 1995 Down; DE CUEVAS et al. 1996 Down; DENG and LIN 1997 Down; DE CUEVAS and SPRADLING 1998 Down).

Bob King was born in New York City in 1928 and received his Ph.D. in Zoology from Yale University in 1952 when he was just 24 years old. After a few years at Brookhaven National Laboratory in Upton, New York, he accepted an assistant professorship in 1956 in the Department of Biology at Northwestern University in Evanston, Illinois. At Northwestern he taught undergraduate and graduate courses in genetics, developmental genetics, cell biology, and cytology and established his long and distinguished research and writing career. He became a full professor in 1964 and is currently an emeritus professor in the Department of Biochemistry, Molecular Biology, and Cell Biology at Northwestern.

Bob has published 117 articles and review articles related to the genetic control of insect oogenesis and is the author, co-author, and editor of several books, including Genetics (Oxford University Press); Handbook of Genetics (Volumes 1–5, Plenum Publishing); six editions of A Dictionary of Genetics (Oxford University Press); Ovarian Development in Drosophila melanogaster (Academic Press); and Insect Ultrastructure (Volumes 1 and 2, Plenum Publishing). He is currently working on the seventh edition of his Dictionary of Genetics, an interdisciplinary reference work that has become the standard supplementary text for students and researchers in classical and molecular genetics. The Dictionary also includes one of the most thorough chronologies of genetic discoveries available in the literature. Bob's varied interests and contributions to interdisciplinary fields are also reflected in his long list of society memberships, among them the American Association for the Advancement of Science (Fellow), the Genetics Society of America, the American Society for Cell Biology (a founding member), the Society for Developmental Biology, and the Histochemical Society.

Bob King is a distinguished scientist who has enhanced scientific knowledge through sheer hard work, as well as a humanist who has embraced people from diverse backgrounds and encouraged and supported those he knows to reach their full potential. Many of his former students have established successful careers of their own—William Klug, Michael Cummings, Elizabeth Koch, Francis Butterworth, and Susanne Gollin among them. His boundless energy, regard for others, and enthusiasm for his work and life in general took him to countries around the world at a time when the world was not quite "a global village." He presented papers at international symposia in Australia, Czechoslovakia, France, and Canada and worked with international scientists in Edinburgh, Tokyo, and Seoul. Students, postdocs, and colleagues were inevitably the beneficiaries of lessons in geography and foreign cultures as an added bonus of his trips abroad. Bob is endowed with a self-effacing sense of humor and great wit. Frank Butterworth recalls a "fly party" where all dressed up as various mutants, but Bob arrived wearing a business suit. Just as his lab thought he had forgotten his costume, Bob took off his jacket to reveal that he had his pants on backward. He was rotated abdomen.

For his vital contributions to the fields of genetics, cell biology, and developmental biology, and for his selfless devotion to students and fellow scientists, Bob King has earned our profound gratitude, our congratulations, and our best wishes.



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*  FOOTNOTES

1 Author e-mail: pkmulligan{at}canada.com Back


*  ACKNOWLEDGMENTS

P.K.M. expresses her gratitude to Allan Spradling and Susanne Gollin for making useful suggestions on an earlier draft of this essay.


*  LITERATURE CITED
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 *LITERATURE CITED

BISHOP, D. L. and R. C. KING, 1984  An ultrastructural study of ovarian development in the otu7 mutant of Drosophila melanogaster.. J. Cell Sci. 67:87-119.[Abstract]

BROWN, E. H. and R. C. KING, 1964  Studies on the events resulting in the formation of an egg chamber in Drosophila melanogaster.. Growth 28:41-81.[Medline]

BUTTERWORTH, F. M., D. BODENSTEIN, and R. C. KING, 1965  Adipose tissue of Drosophila melanogaster. I. An experimental study of larval fat body. J. Exp. Zool. 158:141-154.

CASSIDY, J. D. and R. C. KING, 1969  The dilatable ring canals of the ovarian cystocytes of Habrobracon juglandis.. Biol. Bull. 137:429-437.[Abstract/Free Full Text]

COMER, A. R., L. L. SEARLES, and L. J. KALFAYAN, 1992  Identification of a genomic DNA fragment containing the Drosophila melanogaster ovarian tumor gene (otu) and localization of regions governing its expression. Gene 118:171-179.[Medline]

CUMMINGS, M. R. and R. C. KING, 1969  The cytology of the vitellogenic stages of oogenesis in Drosophila melanogaster.. J. Morphol. 128:427-442.

DABBS, C. K. and R. C. KING, 1980  The differentiation of pseudonurse cells in the ovaries of fs231 females of Drosophila melanogaster.. Int. J. Insect Morphol. Embryol. 9:215-229.

DE CUEVAS, M. and A. C. SPRADLING, 1998  Morphogenesis of the Drosophila fusome and its implication for oocyte specification. Development 125:2781-2789.[Abstract]

DE CUEVAS, M., J. K. LEE, and A. C. SPRADLING, 1996  {alpha}-Spectrin is required for germline cell division and differentiation in the Drosophila ovary. Development 122:3959-3968.[Abstract]

DE CUEVAS, M., M. A. LILLY, and A. C. SPRADLING, 1997  Germline cyst formation in Drosophila.. Annu. Rev. Genet. 31:405-428.[Medline]

DENG, W. and H. LIN, 1997  Spectrosomes and fusomes anchor mitotic spindles during asymmetric germ cell divisions and facilitate the formation of a polarized microtubule array for oocyte specification in Drosophila.. Dev. Biol. 189:79-94.[Medline]

GOLLIN, S. M. and R. C. KING, 1981  Studies of fs(1)1621, a mutation producing ovarian tumors in Drosophila melanogaster.. Dev. Genet. 2:203-218.

JOHNSON, C. C. and R. C. KING, 1974  Oogenesis in the ocelliless mutant of Drosophila melanogaster.. Int. J. Insect Morphol. Embryol. 3:385-395.

JOHNSON, J. H. and R. C. KING, 1972  Studies on fes, a mutation affecting cystocyte cytokinesis in Drosophila melanogaster.. Biol. Bull. 143:525-547.[Abstract/Free Full Text]

KINDERMAN, N. B. and R. C. KING, 1973  Oogenesis in Drosophila virilis. I. Interactions between the ring canal rims and the nucleus of the oocyte. Biol. Bull. 144:331-354.[Abstract/Free Full Text]

KING, R. C., 1960  Oogenesis in adult Drosophila melanogaster. IX. Studies on the cytochemistry and ultrastructure of developing oocytes. Growth 24:265-323.

KING, R. C., 1969  Hereditary ovarian tumors of Drosophila melanogaster.. Natl. Cancer Inst. Monogr. 31:323-345.

KING, R. C., 1970 Ovarian Development in Drosophila melanogaster. Academic Press, New York.

KING, R. C., 1975 The cell cycle and cell differentiation in the Drosophila ovary, pp. 85–109 in Results and Problems in Cell Differentiation, Vol. 7, edited by J. REINERT and H. HOLTZER. Springer-Verlag, Berlin.

KING, R. C., 1979  Aberrant fusomes in the ovarian cystocytes of the fs(1)231 mutant of Drosophila melanogaster.. Int. J. Insect Morphol. Embryol. 8:297-309.

KING, R. C. and H. AKAI, 1971a  Spermatogenesis in Bombyx mori. I. The canal system joining sister spermatocytes. J. Morphol. 134:47-55.

KING, R. C. and H. AKAI, 1971b  Spermatogenesis in Bombyx mori. II. The ultrastructure of synapsed bivalents. J. Morphol. 134:181-194.

KING, R. C. and R. G. BURNETT, 1957  Oogenesis in adult Drosophila melanogaster. V. Mutations which affect nurse cell nuclei. Growth 21:263-280.[Medline]

KING, R. C. and E. A. KOCH, 1963  Studies on the ovarian follicle cells of Drosophila.. Q. J. Microsc. Sci. 104:297-320.

KING, R. C., and J. D. MOHLER, 1975 The genetic analysis of oogenesis in Drosophila, pp. 757–791 in Handbook of Genetics, Vol. 3, edited by R. C. KING. Plenum Publishing, New York.

KING, R. C. and S. F. RILEY, 1982  Ovarian pathologies generated by various alleles of the otu locus in Drosophila melanogaster.. Dev. Genet. 3:69-89.

KING, R. C. and P. D. STORTO, 1988  The role of the otu gene in Drosophila oogenesis. Bioessays 8:18-24.[Medline]

KING, R. C., R. G. BURNETT, and N. A. STALEY, 1957  Oogenesis in adult Drosophila melanogaster. IV. Hereditary ovarian tumors. Growth 21:239-261.

KING, R. C., J. H. SANG, and C. B. LETH, 1961  The hereditary ovarian tumors of the fes mutant of Drosophila melanogaster.. Exp. Cell Res. 23:108-117.[Medline]

KING, R. C., M. BAHNS, R. HOROWITZ, and P. LARRAMENDI, 1978  A mutation that affects female and male germ cells differently in Drosophila melanogaster.. Int. J. Insect Morphol. Embryol. 7:359-375.

KING, R. C., J. D. CASSIDY and A. ROUSSET, 1982 The formation of clones of interconnected cells during gametogenesis in insects, pp. 3–31 in Insect Ultrastructure, Vol. 1, edited by R. C. KING and H. AKAI. Plenum Publishing, New York.

KING, R. C., D. MOHLER, S. F. RILEY, P. D. STORTO, and P. S. NICOLAZZO, 1986  Complementation between alleles at the ovarian tumor locus of Drosophila melanogaster.. Dev. Genet. 7:1-20.[Medline]

KOCH, E. A. and R. C. KING, 1964  Studies on the fes mutant of Drosophila melanogaster.. Growth 28:325-369.

KOCH, E. A. and R. C. KING, 1966  The origin and early differentiation of the egg chamber of Drosophila melanogaster.. J. Morphol. 119:283-304.[Medline]

KOCH, E. A. and R. C. KING, 1969  Further studies on the ring canal system of the ovarian cystocytes of Drosophila melanogaster.. Z. Zellforsch. 102:129-152.[Medline]

KOCH, E. A., P. A. SMITH, and R. C. KING, 1967  The division and differentiation of Drosophila cystocytes. J. Morphol. 121:55-70.[Medline]

LASKO, P. F., 1994 Molecular Genetics of Drosophila Oogenesis, pp. 88–111. R. G. Landes, Austin.

LIN, H. and A. C. SPRADLING, 1993  Germline stem cell division and egg chamber development in transplanted Drosophila germaria. Dev. Biol. 159:140-152.[Medline]

LIN, H. and A. C. SPRADLING, 1995  Fusome asymmetry and oocyte determination in Drosophila.. Dev. Genet. 16:6-12.[Medline]

LIN, H. and A. C. SPRADLING, 1997  A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development 124:2463-2476.[Abstract]

LIN, H., L. YUE, and A. C. SPRADLING, 1994  The Drosophila fusome, a germline-specific organelle, contains membrane skeletal proteins and functions in cyst formation. Development 120:947-956.[Abstract]

MCGRAIL, M. and T. S. HAYS, 1997  The microtubule motor cytoplasmic dynein is required for spindle orientation during germline cell divisions and oocyte differentiation in Drosophila.. Development 124:2409-2419.[Abstract]

MCKEARIN, D., 1997  The Drosophila fusome, organelle biogenesis and germ cell differentiation: if you build it. Bioessays 19:147-152.[Medline]

MCKEARIN, D. and B. OHLSTEIN, 1995  A role for the Drosophila Bag-of-marbles protein in the differentiation of cystoblasts from germline stem cells. Development 121:2937-2947.[Abstract]

MULLIGAN, P. K., J. D. MOHLER, and L. J. KALFAYAN, 1988  Molecular localization and developmental expression of the otu locus of Drosophila melanogaster.. Mol. Cell. Biol. 8:1481-1488.[Abstract/Free Full Text]

RASCH, E. M., R. C. KING, and R. W. RASCH, 1984  Cytophotometric studies on cells from the ovaries of otu mutants of Drosophila melanogaster.. Histochemistry 81:105-110.[Medline]

ROBINSON, D. N. and L. COOLEY, 1996  Stable intercellular bridges in development: the cytoskeleton lining the tunnel. Trends Cell Biol. 6:474-479.[Medline]

RODESCH, C., J. PETTUS, and R. N. NAGOSHI, 1997  The Drosophila ovarian tumor gene is required for the organization of actin filaments during multiple stages in oogenesis. Dev. Biol. 190:153-164.[Medline]

SASS, G. L., J. D. MOHLER, R. C. WALSH, L. J. KALFAYAN, and L. L. SEARLES, 1993  Structure and expression of hybrid dysgenesis-induced alleles of the ovarian tumor (otu) gene in Drosophila melanogaster.. Genetics 133:253-263.[Abstract]

SASS, G. L., A. R. COMER, and L. L. SEARLES, 1995  The ovarian tumor protein isoforms of Drosophila melanogaster exhibit differences in function, expression, and localization. Dev. Biol. 167:201-212.[Medline]

SMITH, P. A. and R. C. KING, 1966  Studies on fused, a mutant gene producing ovarian tumors in Drosophila melanogaster.. J. Natl. Cancer Inst. 36:445-463.

SPRADLING, A. C., 1993 Developmental genetics of oogenesis, pp. 1–70 in The Development of Drosophila melanogaster, edited by M. BATES and A. A. MARTINEZ. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

STEINHAUER, W. R. and L. J. KALFAYAN, 1992  A specific ovarian tumor protein isoform is required for efficient differentiation of germ cells in Drosophila oogenesis. Genes Dev. 6:233-243.[Abstract/Free Full Text]

STEINHAUER, W. R., R. C. WALSH, and L. J. KALFAYAN, 1989  Sequence and structure of the Drosophila melanogaster ovarian tumor gene and generation of an antibody specific for the ovarian tumor protein. Mol. Cell. Biol. 9:5726-5732.[Abstract/Free Full Text]

STORTO, P. D. and R. C. KING, 1987  Fertile heteroallelic combinations of mutant alleles of the otu locus of Drosophila melanogaster.. Roux's Arch. Dev. Biol. 196:210-221.

STORTO, P. D. and R. C. KING, 1988  Multiplicity of functions for the otu gene products during Drosophila oogenesis. Dev. Genet. 9:91-120.[Medline]

STORTO, P. D. and R. C. KING, 1989  The role of polyfusomes in generating branched chains of cystocytes during Drosophila oogenesis. Dev. Genet. 10:70-86.[Medline]

TELFER, W. H., 1975  Development and physiology of the oocyte-nurse cell syncytium. Adv. Insect Physiol. 11:223-319.

XUE, F. and L. COOLEY, 1993  kelch encodes a component of intercellular bridges in Drosophila egg chambers. Cell 72:681-693.[Medline]

YUE, L. and A. C. SPRADLING, 1992  hu-li-tai shao, a gene required for ring canal formation during Drosophila oogenesis, encodes a homolog of adducin. Genes Dev. 6:2443-2454.[Abstract/Free Full Text]