Sequential activation of the EGF receptor pathway during Drosophila oogenesis establishes the dorsoventral axis

Development ◽  
1998 ◽  
Vol 125 (2) ◽  
pp. 191-200 ◽  
Author(s):  
A. Sapir ◽  
R. Schweitzer ◽  
B.Z. Shilo
Keyword(s):  
Target Genes ◽  
Egf Receptor ◽  
Ectopic Expression ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Cell Fates ◽  
Dorsoventral Axis ◽  
Spatial Coordinates ◽  
Sequential Activation

Previous work has demonstrated a role for the Drosophila EGF receptor (Torpedo/DER) and its ligand, Gurken, in the determination of anterioposterior and dorsoventral axes of the follicle cells and oocyte. The roles of DER in establishing the polarity of the follicle cells were examined further, by following the expression of DER-target genes. One class of genes (e.g. kekon) is induced by the DER pathway at all stages. Broad expression of kekon at the stage in which the follicle cells migrate posteriorly over the oocyte, demonstrates the capacity of the pathway to pattern all follicle cells except the ventral-most rows. This may provide the spatial coordinates for the ventral-most follicle cell fates. A second group of target genes (e.g. rhomboid (rho)) is induced only at later stages of oogenesis, and may require additional inputs by signals emanating from the anterior, stretch follicle cells. The function of Rho was analyzed by ectopic expression in the stretch follicle cells, and shown to induce a non-autonomous dorsalizing activity that is independent of Gurken. Rho thus appears to be involved in processing a DER ligand in the follicle cells, to pattern the egg chamber and allow persistent activation of the DER pathway during formation of the dorsal appendages.

The neurogenic locus brainiac cooperates with the Drosophila EGF receptor to establish the ovarian follicle and to determine its dorsal-ventral polarity

Development ◽  
1992 ◽  
Vol 116 (1) ◽  
pp. 177-192 ◽  
Author(s):  
S. Goode ◽  
D. Wright ◽  
A.P. Mahowald
Keyword(s):  
Nurse Cell ◽  
Egf Receptor ◽  
Ovarian Follicle ◽  
Follicle Cell ◽  
Cell Complex ◽  
Follicle Cells ◽  
Sensitive Period ◽  
Cell Fates ◽  
Genetic Mosaic

We have characterized the function of a new neurogenic locus, brainiac (brn), during oogenesis. Homozygous brn females lay eggs with fused dorsal appendages, a phenotype associated with torpedo (top) alleles of the Drosophila EGF receptor (DER) locus. By constructing double mutant females for both brn and top, we have found that brn is required for determining the dorsal-ventral polarity of the ovarian follicle. However, embryos from mature brn eggs develop a neurogenic phenotype which can be zygotically rescued if a wild-type sperm fertilizes the egg. This is the first instance of a Drosophila gene required for determination of dorsal-ventral follicle cell fates that is not required for determination of embryonic dorsal-ventral cell fates. The temperature-sensitive period for brn dorsal-ventral patterning begins at the inception of vitellogenesis. The interaction between brn and DER is also required for at least two earlier follicle cell activities which are necessary to establish the ovarian follicle. Prefollicular cells fail to migrate between each oocyte/nurse cell complex, resulting in follicles with multiple sets of oocytes and nurse cells. brn and DER function is also required for establishing and/or maintaining a continuous follicular epithelium around each oocyte/nurse cell complex. These brn functions as well as the brn requirement for determination of dorsal-ventral polarity appear to be genetically separable functions of the brn locus. Genetic mosaic experiments show that brn is required in the germline during these processes whereas the DER is required in the follicle cells. We propose that brn may be part of a germline signaling pathway differentially regulating successive DER-dependent follicle cell activities of migration, division and/or adhesion and determination during oogenesis. These experiments indicate that brn is required in both tyrosine kinase and neurogenic intercellular signaling pathways. Moreover, the functions of brn in oogenesis are distinct from those of Notch and Delta, two other neurogenic loci that are known to be required for follicular development.

EGF receptor signaling induces pointed P1 transcription and inactivates Yan protein in the Drosophila embryonic ventral ectoderm

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3355-3362 ◽  
Author(s):  
L. Gabay ◽  
H. Scholz ◽  
M. Golembo ◽  
A. Klaes ◽  
B.Z. Shilo ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Egf Receptor ◽  
Protein A ◽  
Drosophila Embryo ◽  
Cell Fates ◽  
Secondary Target ◽  
Graded Activity ◽  
Definition Of

The induction of different cell fates along the dorsoventral axis of the Drosophila embryo requires a graded activity of the EGF receptor tyrosine kinase (DER). Here we have identified primary and secondary target genes of DER, which mediate the determination of discrete ventral cell fates. High levels of DER activation in the ventralmost cells trigger expression of the transcription factors encoded by ventral nervous system defective (vnd) and pointed P1 (pntPl). Concomitant with the induction of pntP1, high levels of DER activity lead to inactivation of the Yan protein, a transcriptional repressor of Pointed-target genes. These two antagonizing transcription factors subsequently control the expression of secondary target genes such as otd, argos and tartan. The simultaneous effects of the DER pathway on pntP1 induction and Yan inactivation may contribute to the definition of the border of the ventralmost cell fates.

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.

Dorsoventral axis formation in Drosophila depends on the correct dosage of the gene gurken

Development ◽  
1994 ◽  
Vol 120 (9) ◽  
pp. 2457-2463 ◽  
Author(s):  
F.S. Neuman-Silberberg ◽  
T. Schupbach
Keyword(s):  
Germ Line ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Limiting Factor ◽  
Axis Formation ◽  
Dorsoventral Patterning ◽  
Wild Type ◽  
Cell Fates ◽  
Dorsoventral Axis ◽  
Signaling Process

The Drosophila gene gurken participates in a signaling process that occurs between the germ line and the somatic cells (follicle cells) of the ovary. This process is required for correct patterning of the dorsoventral axis of both the egg and the embryo. gurken produces a spatially localized transcript which encodes a TGF-alpha-like molecule (Neuman-Silberberg and Schupbach, Cell 75, 165–174, 1993). Mutations in gurken cause a ventralized phenotype in egg and embryo. To determine whether the gurken gene product plays an instructive role in dorsoventral patterning, we constructed females containing extra copies of a gurken transgene. Such females produce dorsalized eggs and embryos, which is expected if gurken acts as a limiting factor in the dorsoventral patterning process. In addition, the expression pattern of the gene rhomboid in the follicle cells is altered in ovaries of females containing extra copies of gurken. Our results indicate that changing gurken dosage in otherwise wild-type ovaries is sufficient to alter the number of somatic follicle cells directed to the dorsal fate. Therefore the gurken-torpedo signaling process plays an instructive role in oogenesis. It induces dorsal cell fates in the follicle cell epithelium and it controls the production of maternal components that will direct the embryonic dorsoventral pattern after fertilization.

Mechanisms of Gurken-dependentpiperegulation and the robustness of dorsoventral patterning inDrosophila

Development ◽  
2002 ◽  
Vol 129 (12) ◽  
pp. 2965-2975 ◽  
Author(s):  
Francesca Peri ◽  
Martin Technau ◽  
Siegfried Roth
Keyword(s):  
Egf Receptor ◽  
Follicle Cell ◽  
Dorsal Side ◽  
Drosophila Embryo ◽  
Follicle Cells ◽  
Follicular Epithelium ◽  
Axis Formation ◽  
Embryonic Patterning ◽  
Cell Fates ◽  
Egg Chamber

The restriction of Pipe, a potential glycosaminoglycan-modifying enzyme, to ventral follicle cells of the egg chamber is essential for dorsoventral axis formation in the Drosophila embryo. pipe repression depends on the TGFα-like ligand Gurken, which activates the Drosophila EGF receptor in dorsal follicle cells. An analysis of Raf mutant clones shows that EGF signalling is required cell-autonomously in all dorsal follicle cells along the anteroposterior axis of the egg chamber to repress pipe. However, the autoactivation of EGF signalling important for dorsal follicle cell patterning has no influence on pipe expression. Clonal analysis shows that also the mirror-fringe cassette suggested to establish a secondary signalling centre in the follicular epithelium is not involved in pipe regulation. These findings support the view that the pipe domain is directly delimited by a long-range Gurken gradient. Pipe induces ventral cell fates in the embryo via activation of the Spätzle/Toll pathway. However, large dorsal patches of ectopic pipe expression induced by Raf clones rarely affect embryonic patterning if they are separated from the endogenous pipe domain. This indicates that potent inhibitory processes prevent pipe dependent Toll activation at the dorsal side of the egg.

maelstrom is required for an early step in the establishment of Drosophila oocyte polarity: posterior localization of grk mRNA

Development ◽  
1997 ◽  
Vol 124 (22) ◽  
pp. 4661-4671 ◽  
Author(s):  
N.J. Clegg ◽  
D.M. Frost ◽  
M.K. Larkin ◽  
L. Subrahmanyan ◽  
Z. Bryant ◽  
...  
Keyword(s):  
Nurse Cell ◽  
Egf Receptor ◽  
Mrna Localization ◽  
Follicle Cells ◽  
Rna Transport ◽  
Nurse Cells ◽  
Loss Of Function ◽  
Cell Fates ◽  
Early Step ◽  
Novel Protein

We describe a mutant, maelstrom, that disrupts a previously unobserved step in mRNA localization within the early oocyte, distinct from nurse-cell-to-oocyte RNA transport. Mutations in maelstrom disturb the localization of mRNAs for Gurken (a ligand for the Drosophila Egf receptor), Oskar and Bicoid at the posterior of the developing (stage 3–6) oocyte. maelstrom mutants display phenotypes detected in gurken loss-of-function mutants: posterior follicle cells with anterior cell fates, bicoid mRNA localization at both poles of the stage 8 oocyte and ventralization of the eggshell. These data are consistent with the suggestion that early posterior localization of gurken mRNA is essential for activation of the Egf receptor pathway in posterior follicle cells. Posterior localization of mRNA in stage 3–6 oocytes could therefore be one of the earliest known steps in the establishment of oocyte polarity. The maelstrom gene encodes a novel protein that has a punctate distribution in the cytoplasm of the nurse cells and the oocyte until the protein disappears in stage 7 of oogenesis.

The relationship between ovarian and embryonic dorsoventral patterning in Drosophila

Development ◽  
1994 ◽  
Vol 120 (8) ◽  
pp. 2245-2257 ◽  
Author(s):  
S. Roth ◽  
T. Schupbach
Keyword(s):  
Egf Receptor ◽  
Germ Line ◽  
Early Embryo ◽  
Follicular Epithelium ◽  
Forming Process ◽  
Cell Fates ◽  
Dorsoventral Axis ◽  
Potential Ligand ◽  
Anterior Posterior ◽  
Anterior Posterior Axis

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.

scholarly journals Establishment of dorsal-ventral polarity of theDrosophilaegg requirescapicuaaction in ovarian follicle cells

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4553-4562 ◽  
Author(s):  
Deborah J. Goff ◽  
Laura A. Nilson ◽  
Donald Morisato
Keyword(s):  
Target Genes ◽  
Nuclear Translocation ◽  
Ovarian Follicle ◽  
Growth Factor Receptor ◽  
Follicle Cell ◽  
Dorsal Side ◽  
Follicle Cells ◽  
Follicular Epithelium ◽  
Egfr Signaling ◽  
Cell Nuclei

The dorsal-ventral pattern of the Drosophila egg is established during oogenesis. Epidermal growth factor receptor (Egfr) signaling within the follicular epithelium is spatially regulated by the dorsally restricted distribution of its presumptive ligand, Gurken. As a consequence, pipe is transcribed in a broad ventral domain to initiate the Toll signaling pathway in the embryo, resulting in a gradient of Dorsal nuclear translocation. We show that expression of pipe RNA requires the action of fettucine (fet) in ovarian follicle cells. Loss of maternal fet activity produces a dorsalized eggshell and embryo. Although similar mutant phenotypes are observed with regulators of Egfr signaling, genetic analysis suggests that fet acts downstream of this event. The fet mutant phenotype is rescued by a transgene of capicua (cic), which encodes an HMG-box transcription factor. We show that Cic protein is initially expressed uniformly in ovarian follicle cell nuclei, and is subsequently downregulated on the dorsal side. Earlier studies described a requirement for cic in repressing zygotic target genes of both the torso and Toll pathways in the embryo. Our experiments reveal that cic controls dorsal-ventral patterning by regulating pipe expression in ovarian follicle cells, before its previously described role in interpreting the Dorsal gradient.

scholarly journals The Function of the Broad-Complex During Drosophila melanogaster Oogenesis

Genetics ◽  
1999 ◽  
Vol 153 (3) ◽  
pp. 1371-1383
Author(s):  
George Tzolovsky ◽  
Wu-Min Deng ◽  
Thomas Schlitt ◽  
Mary Bownes
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Zinc Finger ◽  
Target Genes ◽  
Ectopic Expression ◽  
Follicle Cells ◽  
Chorion Genes ◽  
Broad Complex ◽  
Late Expression

Abstract The Broad-Complex (BR-C) is an early ecdysone response gene that functions during metamorphosis and encodes a family of zinc-finger transcription factors. It is expressed in a dynamic pattern during oogenesis. Its late expression in the lateral-dorsal-anterior follicle cells is related to the morphogenesis of the chorionic appendages. All four zinc-finger isoforms are expressed in oogenesis, which is consistent with the abnormal appendage phenotypes resulting from their ectopic expression. We investigated the mechanism by which the BR-C affects chorion deposition by using BrdU to follow the effects of BR-C misexpression on DNA replication and in situ hybridization to ovarian mRNA to evaluate chorion gene expression. Ectopic BR-C expression leads to prolonged endoreplication and to additional amplification of genes, besides the chorion genes, at other sites in the genome. The pattern of chorion gene expression is not affected along the anterior-posterior axis, but the follicle cells at the anterior of the oocyte fail to migrate correctly in an anterior direction when BR-C is misexpressed. We conclude that the target genes of the BR-C in oogenesis include a protein essential for endoreplication and chorion gene amplification. This may provide a link between steroid hormones and the control of DNA replication during oogenesis.

Determination of the embryonic axes of Drosophila*

Development ◽  
1991 ◽  
Vol 113 (Supplement_1) ◽  
pp. 1-10 ◽  
Author(s):  
Christiane Nüsslein-Volhard
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Spatial Information ◽  
Early Embryo ◽  
Embryonic Axes ◽  
Dorsoventral Axis ◽  
Experimental Approaches ◽  
Combined Action ◽  
Contrast Pattern

The principles of embryonic pattern formation have been studied extensively in many systems using classical experimental approaches. In Drosophila, a powerful combination of genetics and transplantation experiments, as well as molecular biology, have helped to elucidate the mechanisms that operate during oogenesis and early embryogenesis to establish a set of positional cues required for axis determination in the early embryo. In systematic searches for maternal effect mutations a small number of about 30 genes have been identified that specifically affect the process of determination of the embryonic axes. These ‘coordinate’ genes define four systems that determine the anteroposterior (AP) axis (three systems) and the dorsoventral (DV) axis (one system) independently. In the anteroposterior axis, the anterior system determines the segmented region of head and thorax, the posterior system determines the segmented abdominal region, and the terminal system is responsible for the formation of the nonsegmented termini at the anterior and posterior egg tips, the acron and telson. In contrast, pattern along the dorsoventral axis is determined by one system only. Although all four systems use different biochemical mechanisms, they share several properties. (1) The product of one gene in each system is localized in a specific region of the freshly laid egg and functions as a spatial signal. (2) In each system, this spatial information finally results in the asymmetrical distribution of one gene product that functions as a transcription factor. (3) This transcription factor is distributed in a concentration gradient that defines the spatial limits of expression of one or more zygotic target genes. The combined action of these three anteroposterior systems as well as the dorsoventral system defines the expression of zygotic target genes in at least seven distinct regions along the anteroposterior and at least three in the dorsoventral axis. These longitudinal and transverse domains provide a coarse spatial prepattern which is then further refined by the action and interaction of zygotic pattern genes.

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