Organizer activity of the polar cells duringDrosophilaoogenesis

Development ◽  
2002 ◽  
Vol 129 (22) ◽  
pp. 5131-5140 ◽  
Author(s):  
Muriel Grammont ◽  
Kenneth D. Irvine
Keyword(s):  
Cell Fate ◽  
Follicle Cell ◽  
Notch Receptor ◽  
Follicle Cells ◽  
Border Cells ◽  
Genetic Ablation ◽  
Anteroposterior Axis ◽  
Organizer Activity

Patterning of the Drosophila egg requires the establishment of several distinct types of somatic follicle cells, as well as interactions between these follicle cells and the oocyte. The polar cells occupy the termini of the follicle and are specified by the activation of Notch. We have investigated their role in follicle patterning by creating clones of cells mutant for the Notch modulator fringe. This genetic ablation of polar cells results in cell fate defects within surrounding follicle cells. At the anterior, the border cells, the immediately adjacent follicle cell fate, are absent, as are the more distant stretched and centripetal follicle cells. Conversely, increasing the number of polar cells by expressing an activated form of the Notch receptor increases the number of border cells. At the posterior, elimination of polar cells results in abnormal oocyte localization. Moreover, when polar cells are mislocalized laterally, the surrounding follicle cells adopt a posterior fate, the oocyte is located adjacent to them,and the anteroposterior axis of the oocyte is re-oriented with respect to the ectopic polar cells. Our observations demonstrate that the polar cells act as an organizer that patterns surrounding follicle cells and establishes the anteroposterior axis of the oocyte. The origin of asymmetry duringDrosophila development can thus be traced back to the specification of the polar cells during early oogenesis.

Mutations in the Drosophila gene bullwinkle cause the formation of abnormal eggshell structures and bicaudal embryos

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 3023-3033 ◽  
Author(s):  
K.R. Rittenhouse ◽  
C.A. Berg
Keyword(s):  
Cell Migration ◽  
Cell Fate ◽  
Germ Line ◽  
Follicle Cell ◽  
Posterior Pole ◽  
Mirror Image ◽  
Follicle Cells ◽  
Anterior Pole ◽  
Posterior Group ◽  
General Transport

Subcellular localization of gene products and cell migration are both critical for pattern formation during development. The bullwinkle gene is required in Drosophila for disparate aspects of these processes. In females mutant at the bullwinkle locus, the follicle cells that synthesize the dorsal eggshell filaments do not migrate properly, creating short, broad structures. Mosaic analyses demonstrate that wild-type BULLWINKLE function is required in the germ line for these migrations. Since the mRNA for gurken, the putative ligand that signals dorsal follicle cell fate, is correctly localized in bullwinkle mutants, we conclude that our bullwinkle alleles do not affect the dorsoventral polarity of the oocyte and thus must be affecting the follicle cell migrations in some other way. In addition, the embryos that develop from bullwinkle mothers are bicaudal. A KINESIN:beta-GALACTOSIDASE fusion protein is correctly localized to the posterior pole of bullwinkle oocytes during stage 9. Thus, the microtubule structure of the oocyte and general transport along it do not appear to be disrupted prior to cytoplasmic streaming. Unlike other bicaudal mutants, oskar mRNA is localized correctly to the posterior pole of the oocyte at stage 10. By early embryogenesis, however, some oskar mRNA is mislocalized to the anterior pole. Consistent with the mislocalization of oskar mRNA, a fraction of the VASA protein and nanos mRNA are also mislocalized to the anterior pole of bullwinkle embryos. Mislocalization of nanos mRNA to the anterior is dependent on functional VASA protein. Although the mirror-image segmentation defects appear to result from the action of the posterior group genes, germ cells are not formed at the anterior pole. The bicaudal phenotype is also germ-line dependent for bullwinkle. We suspect that BULLWINKLE interacts with the cytoskeleton and extracellular matrix and is necessary for gene product localization and cell migration during oogenesis after stage 10a.

Drosophila bunched integrates opposing DPP and EGF signals to set the operculum boundary

Development ◽  
2000 ◽  
Vol 127 (4) ◽  
pp. 745-754 ◽  
Author(s):  
L.L. Dobens ◽  
J.S. Peterson ◽  
J. Treisman ◽  
L.A. Raftery
Keyword(s):  
Cell Fate ◽  
Egf Receptor ◽  
Ovarian Follicle ◽  
Ectopic Expression ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Sharp Boundary ◽  
Smad Protein ◽  
Multiple Cell ◽  
Egf Signaling

The Drosophila BMP homolog DPP can function as a morphogen, inducing multiple cell fates across a developmental field. However, it is unknown how graded levels of extracellular DPP are interpreted to organize a sharp boundary between different fates. Here we show that opposing DPP and EGF signals set the boundary for an ovarian follicle cell fate. First, DPP regulates gene expression in the follicle cells that will create the operculum of the eggshell. DPP induces expression of the enhancer trap reporter A359 and represses expression of bunched, which encodes a protein similar to the mammalian transcription factor TSC-22. Second, DPP signaling indirectly regulates A359 expression in these cells by downregulating expression of bunched. Reduced bunched function restores A359 expression in cells that lack the Smad protein MAD; ectopic expression of BUNCHED suppresses A359 expression in this region. Importantly, reduction of bunched function leads to an expansion of the operculum and loss of the collar at its boundary. Third, EGF signaling upregulates expression of bunched. We previously demonstrated that the bunched expression pattern requires the EGF receptor ligand GURKEN. Here we show that activated EGF receptor is sufficient to induce ectopic bunched expression. Thus, the balance of DPP and EGF signals sets the boundary of bunched expression. We propose that the juxtaposition of cells with high and low BUNCHED activity organizes a sharp boundary for the operculum fate.

Ectopic activation of torpedo/Egfr, a Drosophila receptor tyrosine kinase, dorsalizes both the eggshell and the embryo

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3871-3880 ◽  
Author(s):  
A.M. Queenan ◽  
A. Ghabrial ◽  
T. Schupbach
Keyword(s):  
Cell Fate ◽  
Growth Factor Receptor ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Follicular Epithelium ◽  
Cell Fates ◽  
Egfr Activation ◽  
Egg Chamber ◽  
Anterior Posterior ◽  
Anterior Posterior Axis

The Drosophila gene torpedo/Egfr (top/Egfr) encodes a homolog of the vertebrate Epidermal Growth Factor receptor. This receptor is required several times during the life cycle of the fly for the transmisson of developmental cues. During oogenesis, Top/Egfr activation is required for the establishment of the dorsal/ventral axis of the egg and the embryo. To examine how ectopic Top/Egfr activation affects cell fate determination, we constructed an activated version of the protein. Expression of this activated form (lambda top) in the follicle cells of the ovary induces dorsal cell fates in both the follicular epithelium and the embryo. Different levels of expression resulted in different dorsal follicle cell fates. These dorsal cell fates were expanded in the anterior, but not the posterior, of the egg, even in cases where all the follicle cells covering the oocyte expressed lambda top. The expression of genes known to respond to top/Egfr activation, argos (aos), kekkon1 (kek 1) and rhomboid (rho), was also expanded in the presence of the lambda top construct. When lambda top was expressed in all the follicle cells covering the oocyte, kek 1 and argos expression was induced in follicle cells all along the anterior/posterior axis of the egg chamber. In contrast, rho RNA expression was only activated in the anterior of the egg chamber. These data indicate that the response to Top/Egfr signaling is regulated by an anterior/posterior prepattern in the follicle cells. Expression of lambda top in the entire follicular epithelium resulted in an embryo dorsalized along the entire anterior/posterior axis. Expression of lambda top in anterior or posterior subpopulations of follicle cells resulted in regionally autonomous dorsalization of the embryos. This result indicates that subpopulations of follicle cells along the anterior/posterior axis can respond to Top/Egfr activation independently of one another.

scholarly journals fs (1) Yb is required for ovary follicle cell differentiation in Drosophila melanogaster and has genetic interactions with the Notch group of neurogenic genes.

Genetics ◽  
1995 ◽  
Vol 140 (1) ◽  
pp. 207-217 ◽  
Author(s):  
E Johnson ◽  
S Wayne ◽  
R Nagoshi
Keyword(s):  
Cell Fate ◽  
Ovarian Follicle ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Female Sterility ◽  
Specific Factor ◽  
Temperature Sensitive ◽  
Egg Maturation ◽  
Egg Chambers ◽  
Mutant Phenotypes

Abstract Phenotypic and genetic analyses demonstrate that fs (1) Yb activity is required in the soma for the development of a subset of ovarian follicle cells and to support later stages of egg maturation. Mutations in fs (1) Yb cause a range of ovarian phenotypes, from the improper segregation of egg chambers to abnormal dorsal appendage formation. The mutant phenotypes associated with fs (1) Yb are very similar to the ovarian aberrations produced by temperature-sensitive alleles of Notch and Delta. Possible functional or regulatory interactions between fs (1) Yb and Notch are suggested by genetic studies. A duplication of the Notch locus partially suppresses the female-sterility caused by fs (1) Yb mutations, while reducing Notch dosage makes the fs (1) Yb mutant phenotype more severe. In addition, fs (1) Yb alleles also interact with genes that are known to act with or regulate Notch activity, including Delta, daughterless, and mastermind. However, differences between the mutant ovarian phenotype of fs (1) Yb and that of Notch or Delta indicate that the genes do not have completely overlapping functions in the ovary. We propose that fs (1) Yb acts as an ovary-specific factor that determines follicle cell fate.

The eggshell of Drosophila melanogaster. V. Structure and morphogenesis of the micropylar apparatus

1986 ◽  
Vol 64 (11) ◽  
pp. 2509-2519 ◽  
Author(s):  
Flora E. Zarani ◽  
Lukas H. Margaritis
Keyword(s):  
Drosophila Melanogaster ◽  
Outer Part ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Vitelline Membrane ◽  
Mature Stage ◽  
Border Cells ◽  
Border Cell ◽  
Paracrystalline Structure ◽  
Cell Subpopulations

The micropylar apparatus in Drosophila melanogaster consists of two parts. The inner part is a protrusion of vitelline membrane, whereas the outer part is a chorionic protrusion containing a canal, through which the spermatozoon enters. In the formation of the micropylar apparatus two follicle cell subpopulations are involved: the border cells, i.e., a group of 9 follicle cells, and the peripheral cells (about 36 cells). The morphogenesis of the micropyle starts at stage 10B, when the border cells secrete the paracrystalline region of the vitelline membrane. The micropylar canal (length 7 μm, diameter 0.7 μm) and the pocket that penetrates within the paracrystalline structure are moulded by two border cell projections, full of microtubules. The formation of the micropyle terminates at stage 14B, when its chorionic part is completed and the border cell projections degenerate. The structure of the micropyle in fertilized and unfertilized laid eggs differs from the mature (stage 14B) egg in that the vitelline membrane is modified and appears homogeneous as in the rest of the eggshell. These transformations seem to be unrelated to sperm entry.

Pointed, an ETS domain transcription factor, negatively regulates the EGF receptor pathway in Drosophila oogenesis

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 3745-3754 ◽  
Author(s):  
A.M. Morimoto ◽  
K.C. Jordan ◽  
K. Tietze ◽  
J.S. Britton ◽  
E.M. O'Neill ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Egf Receptor ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Dorsal Region ◽  
Epidermal Growth ◽  
Ets Domain ◽  
Ets Transcription Factor ◽  
Midline Cells

Spatially regulated activation of the Drosophila epidermal growth factor (EGF) receptor by its ligand, Gurken, is required for establishment of the dorsal/ventral axis of the oocyte and embryo. During mid-oogenesis, Gurken is concentrated at the dorsal-anterior of the oocyte and is thought to activate the EGF receptor pathway in adjacent follicle cells. In response to this signal, dorsal follicle cell fate is determined. These cells further differentiate into either appendage-producing or midline cells, resulting in patterning in the dorsal follicle cell layer. We show here that Pointed, an ETS transcription factor, is required in dorsal follicle cells for this patterning. Loss of pointed results in the loss of midline cells and an excess of appendage-forming cells, a phenotype associated with overactivation of the EGF receptor pathway in the dorsal region. Overexpression of pointed leads to a phenotype similar to that generated by loss of the EGF receptor pathway. This suggests that Pointed normally down-regulates EGF receptor signaling in the midline to generate patterning in the dorsal region. Interestingly, pointed expression is induced by the EGF receptor pathway. These data indicate a novel antagonistic function for Pointed in oogenesis; in response to activation of the EGF receptor, pointed is expressed and negatively regulates the EGF receptor pathway, possibly by integrating information from a second pathway.

scholarly journals hold up Is Required for Establishment of Oocyte Positioning, Follicle Cell Fate and Egg Polarity and Cooperates with Egfr during Drosophila Oogenesis

Genetics ◽  
1998 ◽  
Vol 148 (2) ◽  
pp. 767-773
Author(s):  
Deborah Rotoli ◽  
Silvia Andone ◽  
Claudia Tortiglione ◽  
Andrea Manzi ◽  
Carla Malva ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Layer ◽  
Growth Factor Receptor ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Early Event ◽  
Parallel Pathway ◽  
Egg Chambers ◽  
Molecular Machinery ◽  
Epidermal Growth

Abstract In Drosophila the posterior positioning of the oocyte within the germline cluster defines the initial asymmetry during oogenesis. From this early event, specification of both body axes is controlled through reciprocal signaling between germline and soma. Here it is shown that the mutation hold up (hup) affects oocyte positioning in the egg chamber, follicle cell fate and localization of different markers in the growing oocytes. This occurs not only in dicephalic egg chambers, but also in oocytes normally located at the posterior. Generation of mosaic egg chambers indicates that hup has to be at least somatically required. Possible interactions of hup with Egfr, the Drosophila epidermal growth factor receptor homolog, have been investigated in homozygous double mutants constructed by recombination. Stronger new ovarian phenotypes have been obtained, the most striking being accumulation of follicle cells in multiple layers posteriorly to the oocyte. It is proposed that the hup gene product is a component of the molecular machinery that leads to the establishment of polarity both in follicle cell layer and oocyte, acting in the same or in a parallel pathway of Egfr.

scholarly journals Modeling Notch-Induced Tumor Cell Survival in the Drosophila Ovary Identifies Cellular and Transcriptional Response to Nuclear NICD Accumulation

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2222
Author(s):  
Allison Jevitt ◽  
Yi-Chun Huang ◽  
Su-Mei Zhang ◽  
Deeptiman Chatterjee ◽  
Xian-Feng Wang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Survival ◽  
Rna Sequencing ◽  
Tumor Model ◽  
Follicle Cell ◽  
Notch Receptor ◽  
Follicle Cells ◽  
Follicular Epithelium ◽  
Nuclear Accumulation ◽  
The Impact

Notch is a conserved developmental signaling pathway that is dysregulated in many cancer types, most often through constitutive activation. Tumor cells with nuclear accumulation of the active Notch receptor, NICD, generally exhibit enhanced survival while patients experience poorer outcomes. To understand the impact of NICD accumulation during tumorigenesis, we developed a tumor model using the Drosophila ovarian follicular epithelium. Using this system we demonstrated that NICD accumulation contributed to larger tumor growth, reduced apoptosis, increased nuclear size, and fewer incidents of DNA damage without altering ploidy. Using bulk RNA sequencing we identified key genes involved in both a pre- and post- tumor response to NICD accumulation. Among these are genes involved in regulating double-strand break repair, chromosome organization, metabolism, like raptor, which we experimentally validated contributes to early Notch-induced tumor growth. Finally, using single-cell RNA sequencing we identified follicle cell-specific targets in NICD-overexpressing cells which contribute to DNA repair and negative regulation of apoptosis. This valuable tumor model for nuclear NICD accumulation in adult Drosophila follicle cells has allowed us to better understand the specific contribution of nuclear NICD accumulation to cell survival in tumorigenesis and tumor progression.

scholarly journals Drosophila Notch receptor activity suppresses Hairless function during adult external sensory organ development.

Genetics ◽  
1995 ◽  
Vol 141 (4) ◽  
pp. 1491-1505
Author(s):  
D F Lyman ◽  
B Yedvobnick
Keyword(s):  
Cell Fate ◽  
Daughter Cell ◽  
Notch Receptor ◽  
Sensory Organ ◽  
Cell Fates ◽  
Gain Of Function ◽  
Over Expression ◽  
Cell Fate Decisions ◽  
Synergistic Enhancement ◽  
Conditional Expression

Abstract The neurogenic Notch locus of Drosophila encodes a receptor necessary for cell fate decisions within equivalence groups, such as proneural clusters. Specification of alternate fates within clusters results from inhibitory communication among cells having comparable neural fate potential. Genetically, Hairless (H) acts as an antagonist of most neurogenic genes and may insulate neural precursor cells from inhibition. H function is required for commitment to the bristle sensory organ precursor (SOP) cell fate and for daughter cell fates. Using Notch gain-of-function alleles and conditional expression of an activated Notch transgene, we show that enhanced signaling produces H-like loss-of-function phenotypes by suppressing bristle SOP cell specification or by causing an H-like transformation of sensillum daughter cell fates. Furthermore, adults carrying Notch gain of function and H alleles exhibit synergistic enhancement of mutant phenotypes. Over-expression of an H+ transgene product suppressed virtually all phenotypes generated by Notch gain-of-function genotypes. Phenotypes resulting from over-expression of the H+ transgene were blocked by the Notch gain-of-function products, indicating a balance between Notch and H activity. The results suggest that H insulates SOP cells from inhibition and indicate that H activity is suppressed by Notch signaling.

scholarly journals Notch Signaling Regulation in HCC: From Hepatitis Virus to Non-Coding RNAs

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 521
Author(s):  
Catia Giovannini ◽  
Francesca Fornari ◽  
Fabio Piscaglia ◽  
Laura Gramantieri
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Hepatitis Virus ◽  
Notch Pathway ◽  
Notch Receptor ◽  
Gamma Secretase ◽  
Stem Cell Maintenance ◽  
Pathway Activation ◽  
Promising Therapeutic Approach ◽  
Conserved Genes

The Notch family includes evolutionary conserved genes that encode for single-pass transmembrane receptors involved in stem cell maintenance, development and cell fate determination of many cell lineages. Upon activation by different ligands, and depending on the cell type, Notch signaling plays pleomorphic roles in hepatocellular carcinoma (HCC) affecting neoplastic growth, invasion capability and stem like properties. A specific knowledge of the deregulated expression of each Notch receptor and ligand, coupled with resultant phenotypic changes, is still lacking in HCC. Therefore, while interfering with Notch signaling might represent a promising therapeutic approach, the complexity of Notch/ligands interactions and the variable consequences of their modulations raises concerns when performed in undefined molecular background. The gamma-secretase inhibitors (GSIs), representing the most utilized approach for Notch inhibition in clinical trials, are characterized by important adverse effects due to the non-specific nature of GSIs themselves and to the lack of molecular criteria guiding patient selection. In this review, we briefly summarize the mechanisms involved in Notch pathway activation in HCC supporting the development of alternatives to the γ-secretase pan-inhibitor for HCC therapy.

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