Intercellular signaling and the polarization of body axes during Drosophila oogenesis.
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Animals↗
Biomedical subjects
T Schüpbach
Publications and source records attributed to T Schüpbach.
The Drosophila TGF-alpha-like protein Gurken: expression and cellular localization during Drosophila oogenesis.
The establishment of anterior-posterior and dorsal-ventral polarity of the Drosophila egg and embryo depends on the function of the genes gurken, cornichon and Egfr (Drosophila epidermal growth factor receptor homolog). These genes encode components of a signal transduction pathway that transmits information between the germline cells and the somatic follicle cells of the ovary. gurken encodes a transforming growth factor-alpha-like protein and is a putative germline ligand of the Egfr present on the follicle cells. In mid-oogenesis the gurken transcript becomes spatially localized to the future dorsal-anterior cortex of the oocyte. To analyze the distribution pattern of Gurken protein we prepared antibodies against Gurken. We describe here the distribution pattern of the Gurken protein in wild-type ovaries and in ovaries from a number of dorsal-ventral patterning mutants. By immunoblotting we detect one major form of the Gurken protein, which likely corresponds to the unprocessed protein.
Animals↗
Encore, a gene required for the regulation of germ line mitosis and oocyte differentiation during Drosophila oogenesis.
During Drosophila oogenesis, a stem cell daughter undergoes precisely four rounds of mitosis to generate a cyst of 16 cells interconnected by cytoplasmic bridges. One of the cells becomes the oocyte while the remaining 15 cells differentiate as nurse cells. We hve identified a gene, encore, that is involved both in regulating the number of germline mitoses and in the process of oocyte differentation. Mutations in encore result in exactly one extra round of mitosis in the germline. Genetic and molecular studies indicate that this mitotic defect may be mediated through the gene bag-of-marbles. The isolation and characterization of multiple alleles of encore revealed that they were all temperature sensitive for this phenotype. Mutations in encore also affect the process of oocyte differentiation. Egg chambers are produced in which the oocyte nucleus has undergone endoreplication often resulting in the formation of 16 nurse cells. We argue that these two phenotypes produced by mutations in encore represent two independent requirements for encore during oogenesis.
Alleles↗
cornichon and the EGF receptor signaling process are necessary for both anterior-posterior and dorsal-ventral pattern formation in Drosophila.
In Drosophila, the dorsal-ventral polarity of the egg chamber depends on the localization of the oocyte nucleus and the gurken RNA to the dorsal-anterior corner of the oocyte. Gurken protein presumably acts as a ligand for the Drosophila EGF receptor (torpedo/DER) expressed in the somatic follicle cells surrounding the oocyte. cornichon is a gene required in the germline for dorsal-ventral signaling. cornichon, gurken, and torpedo also function in an earlier signaling event that establishes posterior follicle cell fates and specifies the anterior-posterior polarity of the egg chamber. Mutations in all three genes prevent the formation of a correctly polarized microtubule cytoskeleton required for proper localization of the anterior and posterior determinants bicoid and oskar and for the asymmetric positioning of the oocyte nucleus.
Amino Acid Sequence↗
Dorsoventral patterning in Drosophila oogenesis.
Dorsoventral polarity in the egg chamber of Drosophila involves the localization of maternal gurken RNA to the dorsal side of the oocyte. The gurken protein has homology to secreted growth factors and may bind to the torpedo/DER receptor tyrosine kinase present on the adjacent follicle cells. This localized signal from the oocyte to the follicle cells appears to initiate a cascade of events leading to dorsal follicle cell differentiation, and delimiting and orienting the future dorsoventral axis of the embryo.
Animals↗
Molecular analysis of the Drosophila EGF receptor homolog reveals that several genetically defined classes of alleles cluster in subdomains of the receptor protein.
Mutations in the torpedo gene, which encodes the fruitfly homolog of the epidermal growth factor receptor (DER), disrupt a variety of developmental processes in Drosophila. These include the survival of certain embryonic ectodermal tissues, the proliferation of the imaginal discs, the morphogenesis of several adult ectodermal structures and oogenesis, torpedo is genetically complex: a number of alleles of the gene differentially affect the development of specific tissues, such as the eye, wing, bristles and ovary. In addition, torpedo mutations exhibit interallelic complementation. Molecular analysis of 24 loss-of-function mutations in the torpedo gene provides insights into the mechanistic basis of its genetic complexity. We observe an intriguing correlation between molecular lesions and mutant phenotypes. Alleles that differentially affect specific developmental processes encode receptors with altered extracellular domains. Alleles that fully or partially complement a wide range of embryonic and postembryonic torpedo mutations encode receptors with altered intracellular domains. From these findings we conclude the following. First, the torpedo protein may be activated by tissue-specific ligands. Second, the torpedo receptor tyrosine kinase may phosphorylate multiple substrates. Third, signal transduction by torpedo appears to require the physical association of receptors. Finally, the extracellular domain of the Torpedo protein may play an essential role in mediating receptor-receptor interactions.
Alleles↗
The relationship between ovarian and embryonic dorsoventral patterning in Drosophila.
In Drosophila, the dorsoventral asymmetry of the egg chamber depends on a dorsalizing signal that emanates from the oocyte. This signal is supplied by the TGF alpha-like gurken protein whose RNA is localized to the dorsal-anterior corner of the oocyte, gurken protein is the potential ligand of the Drosophila EGF receptor homolog (torpedo), which is expressed in the follicular epithelium surrounding the oocyte. Here, we describe how changes in the dorsalizing germ-line signal affect the embryonic dorsoventral pattern. A reduction in strength of the germ-line signal as produced by mutations in gurken or torpedo does not change the slope of the embryonic dorsoventral morphogen gradient, but causes a splitting of the gradient ventrally. This leads to embryos with two partial dorsoventral axes. A change in distribution of the germ-line signal as caused by fs(1)K10, squid and orb mutations leads to a shift in the orientation of the embryonic dorsoventral axis relative to the anterior-posterior axis. In extreme cases, this results in embryos with a dorsoventral axis almost parallel to the anterior-posterior axis. These results imply that gurken, unlike other localized cytoplasmic determinants, is not directly responsible for the establishment of cell fates along a body axis, but that it restricts and orients an active axis-forming process which occurs later in the follicular epithelium or in the early embryo.
Animals↗
The Drosophila dorsoventral patterning gene gurken produces a dorsally localized RNA and encodes a TGF alpha-like protein.
Cell-cell interactions in the Drosophila ovary play a crucial role in the establishment of dorsoventral polarity of both the egg shell and the future embryo. Torpedo/DER (top/DER), a homolog of the vertebrate epidermal growth factor receptor, is required for this signaling process in the somatic cells of the ovary. In contrast, gurken (grk), which also functions in this pathway, is required in the germline. We cloned the grk gene and found that it encodes a TGF alpha-like protein. Grk is, therefore, likely to be a ligand of top/DER, activating the receptor during oogenesis. During oogenesis, the grk transcript becomes asymmetrically localized to the dorsal corner of the oocyte. We propose that the dorsal localization of grk RNA results in a spatially restricted ligand that asymmetrically activates the receptor.
Alleles↗
The torpedo (DER) receptor tyrosine kinase is required at multiple times during Drosophila embryogenesis.
The torpedo (DER) gene of Drosophila, which encodes a receptor tyrosine kinase of the EGF receptor subfamily, is essential for oogenesis, embryogenesis and imaginal disc development. To gain insight into the nature of the signals transduced by the torpedo product, we have characterized the gene's loss-of-function phenotype in the embryo. Through the induction of germline clones, we provide a genetic demonstration that maternal torpedo product does not contribute to zygotic development. Thus, the embryonic lethal phenotypes examined accurately reflect the consequences of eliminating all gene activity from the zygote. Temperature-shift experiments with the conditional allele topIF26 show that torpedo is required at two distinct times during embryonic development: the gene is first needed for germband retraction and for the production of anterior, posterior and ventral cuticle, then later for the secretion of ventral denticles. Since denticle formation can be severely disrupted in topIF26 animals without affecting cuticle production, the early and late requirements for torpedo appear to be functionally unrelated. torpedo, therefore, is required at multiple times in the development of the ventral epidermis, and may transduce qualitatively different signals. Since the early requirement for torpedo correlates with the first visible defect in embryonic development, increased cell death in the amnioserosa, cephalic ectoderm and ventral epidermis, the abnormalities in cuticle production and germband shortening seen in the mutant may be secondary consequences of a primary defect in cell viability. Given that the onset of cell death in torpedo embryos is not preceded by any obvious defects in mitogenesis, the establishment of cell identities or the maintenance of gene expression, it is possible that torpedo transduces a signal necessary for cell survival per se during early embryogenesis. During late embryogenesis, torpedo may mediate the reception of a second signal which regulates ventral epidermal cell differentiation.
Animals↗
Female sterile mutations on the second chromosome of Drosophila melanogaster. II. Mutations blocking oogenesis or altering egg morphology.
In mutagenesis screens for recessive female sterile mutations on the second chromosome of Drosophila melanogaster 528 lines were isolated which allow the homozygous females to survive but cause sterility. In 62 of these lines early stages of oogenesis are affected, and these females usually do not lay any eggs. In 333 lines oogenesis proceeds apparently normally to stage 8 of oogenesis, but morphological defects become often apparent during later stages of oogenesis, and are visible in the defective eggs produced by these females whereas 133 lay eggs that appear morphologically normal, but do not support normal embryonic development. Of the lines 341 have been genetically characterized and define a total of 140 loci on the second chromosome. Not all the loci are specific for oogenesis. From the numbers obtained we estimate that the second chromosome of Drosophila contains about 13 loci that are relatively specific for early oogenesis, 70 loci that are specifically required in mid to late oogenesis, and around 30 maternal-effect lethals.
Animals↗
The maternal ventralizing locus torpedo is allelic to faint little ball, an embryonic lethal, and encodes the Drosophila EGF receptor homolog.
The torpedo gene of Drosophila melanogaster is involved in the establishment of the dorsoventral pattern of eggshell and embryo. We have isolated new alleles of torpedo and have found that torpedo is allelic to the zygotic embryonic lethal faint little ball. We have shown that torpedo resides in subdivision 57F on the second chromosome--at the same location as the Drosophila homolog of the EGF receptor (DER). Using a cosmid that contains most of the DER coding region as a hybridization probe, we have shown that a cytologically small deficiency that eliminates torpedo activity also removes the DER gene, and that an inversion that was isolated as a strong torpedo allele breaks the coding region of the DER gene. We conclude that torpedo is the DER gene.
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The egg came first, of course! Anterior-posterior pattern formation in Drosophila embryogenesis and oogenesis.
The anterior-posterior body pattern of the Drosophila embryo is initiated through the action of maternal gene products. In particular, three groups of maternally acting genes (the anterior, posterior and terminal groups) have been shown to direct the synthesis and spatial restriction of the three major organizing activities in the egg. The initial spatial localizations of the maternal organizing activities are established during oogenesis. After fertilization these activities regulate zygotic gene activity along the anterior-posterior axis of the egg.
Animals↗
Female sterile mutations on the second chromosome of Drosophila melanogaster. I. Maternal effect mutations.
In mutagenesis screens for recessive female sterile mutations on the second chromosome of Drosophila melanogaster 529 chromosomes were isolated which allow the homozygous females to survive, but cause them to be sterile. In 136 of these lines, mutant females produce morphologically normal eggs which cannot support normal embryonic development. These "maternal-effect" mutations fall into 67 complementation groups which define 23 multiply hit and 44 singly hit loci. In eggs from 14 complementation groups development is blocked before the formation of a syncytial blastoderm. In eggs from 12 complementation groups development is abnormal before cellularization, 17 complementation groups cause abnormal cellularization, 12 complementation groups cause changes in cellular morphology in early gastrulation stages, and 12 complementation groups seem to affect later embryonic development.
Animals↗
Coordinately and differentially mutable activities of torpedo, the Drosophila melanogaster homolog of the vertebrate EGF receptor gene.
The torpedo (top) locus of Drosophila encodes the fruitfly homolog of the vertebrate epidermal growth factor receptor gene and the neu proto-oncogene. We have isolated 13 top alleles in a screen for mutations failing to complement the female sterility of top, a recessive maternal effect allele that disrupts the establishment of the dorsoventral pattern of the egg shell and embryo. Several alleles recovered in this screen are zygotic lethal mutations; genetic analysis of these alleles has demonstrated that top is allelic to the embryonic lethal locus faint little ball. The 13 mutations recovered in our screens and 19 previously isolated top alleles have been genetically characterized through complementation tests with a series of hypomorphic and amorphic alleles. Nearly every top allele fails to complement the maternal effect sterility of top. Complementation tests show that the gene is required not only for oogenesis and embryogenesis, but also for pupal viability, for the growth of certain imaginal discs and for the patterning of specific ectodermal derivatives of the imaginal discs. Complementation analysis further demonstrates that the top lesions can be divided into general phenotypic categories: alleles affecting all gene activities in a coordinate manner, alleles preferentially affecting embryogenesis, alleles preferentially retaining oogenesis activity and alleles differentially affecting the development of specific imaginal disc derivatives. Correlations observed between the various developmental defects produced by top lesions suggest that the gene possesses several differentially, though not independently, mutable activities.
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cappuccino and spire: two unique maternal-effect loci required for both the anteroposterior and dorsoventral patterns of the Drosophila embryo.
cappuccino and spire are unique Drosophila maternal-effect loci that participate in pattern formation in both the anteroposterior and dorsoventral axes of the early embryo. Mutant females produce embryos lacking pole cells, polar granules, and normal abdominal segmentation. They share these defects with the posterior group of maternal-effect genes. Although embryos are defective in abdominal segmentation, in double mutant combinations with Bicaudal D, abdominal segments can be formed in the anterior half of the egg. This indicates that embryos produced by mutant females contain the 'posterior determinant' required for abdominal segmentation (Nüsslein-Volhard et al. 1987) and suggests that the wild-type gene products are not required for production of the posterior determinant but, rather, for its localization or stabilization. The vasa protein, a component of polar granules, is not localized at the posterior pole of mutant egg chambers or embryos, providing additional support for the hypothesis that localization to or stabilization of substances at the posterior pole of the egg chamber is defective in mutant females. Females mutant for the strongest alleles also produce dorsalized embryos. Phenotypic analysis reveals that these dorsalized embryos also have abdominal segmentation defects. The mutant phenotypes can be ordered in a series of increasing severity. Pole cell formation is most sensitive to loss of functional gene products, followed by abdominal segmentation, whereas normal dorsoventral patterning is the least sensitive to loss of functional gene products. In addition, mutant females contain egg chambers that appear to be dorsalized, resulting in the production of eggs with dorsalized eggshells. Germ-line mosaics indicate that cappuccino and spire are required in the oocyte-nurse cell complex. This suggests that the eggshell phenotype results from altered pattern in the underlying germ cell. Also, we defined the epistatic relationships between several early patterning loci, on the basis of an analysis of the eggs and embryos produced by females doubly mutant for cappuccino or spire and other loci that affect the pattern of both the egg and the embryo. On the basis of our current knowledge of the genes involved in this process, we formulated a working model for the early steps in dorsoventral patterning.
Animals↗
Germ line and soma cooperate during oogenesis to establish the dorsoventral pattern of egg shell and embryo in Drosophila melanogaster.
Mutations in gurken and torpedo cause a ventralization in the follicle cell epithelium during Drosophila oogenesis and in the pattern of the embryo that develops in the resultant egg. Both genes lie midway in an epistatic series between fs(1)K10 and dorsal; the mutations block the dorsalization normally observed in K10 eggs but have no effect on the phenotype of embryos derived from dorsal mothers. Analysis of germ-line mosaics demonstrates that both ovarian and embryonic phenotypes will be produced when either the gurken+ gene is removed from the germ line or torpedo+ is removed from the soma. This shows that the dorsoventral pattern of the Drosophila egg chamber depends on the transfer of spatial information from the germ line to the somatic follicle cells, and from somatic cells to the oocyte.
Animals↗
Normal female germ cell differentiation requires the female X chromosome to autosome ratio and expression of sex-lethal in Drosophila melanogaster.
In somatic cells of Drosophila, the ratio of X chromosomes to autosomes (X:A ratio) determines sex and dosage compensation. The present paper addresses the question of whether germ cells also use the X:A ratio for sex determination and dosage compensation. Triploid female embryos were generated which, through the loss of an unstable ring-X chromosome, contained some germ cells of 2X;3A constitution in their ovaries. Such germ cells were shown to differentiate along one of two alternative pathways: a minority developed into normal female oocytes and eggs; the majority developed into abnormal multicellular cysts. An X:A ratio of 1 is, therefore, required in female germ cell development, at least in the mature ovary after stem cell division. Abnormal development of female germ cells was also observed when 2X;2A germ cells which were homozygous or trans-heterozygous for mutant alleles at the Sex-lethal locus were transplanted into normal female host embryos at the blastoderm stage. Germ cells homozygous for amorphic alleles failed to give rise to normal eggs. Instead, they formed multicellular cysts, very similar to those formed by 2X;3A cells. Zygotic Sxl+ activity is, therefore, also necessary for the development of normal female germ cells. No abnormalities were detected in transplanted germ cells from female embryos whose mothers had been homozygous for the mutation daughterless. When normal XY germ cells were transplanted into female embryos, no traces of such cells could be found in the adult ovary. XY germ cells seem, therefore, not to develop as far as 2X;3A or Sxl homozygous cells in a female gonad. This indicates that neither 2X;3A nor Sxl homozygous germ cells are equivalent to normal XY germ cells.
Animals↗
Autosomal mutations that interfere with sex determination in somatic cells of Drosophila have no direct effect on the germline.
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