scholarly journals The ETS-transcription factor Pointed is sufficient to regulate the posterior fate of the follicular epithelium

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev189787
Author(s):  
Cody A. Stevens ◽  
Nicole T. Revaitis ◽  
Rumkan Caur ◽  
Nir Yakoby
Keyword(s):  
Transcription Factor ◽  
Growth Factor Receptor ◽  
Bmp Signaling ◽  
Janus Kinase ◽  
Follicle Cells ◽  
Follicular Epithelium ◽  
T Box ◽  
Border Cell ◽  
Morphogenetic Protein ◽  
Ets Transcription Factor

ABSTRACTThe Janus-kinase/signal transducer and activator of transcription (JAK/STAT) pathway regulates the anterior posterior axis of the Drosophila follicle cells. In the anterior, it activates the bone morphogenetic protein (BMP) signaling pathway through expression of the BMP ligand decapentaplegic (dpp). In the posterior, JAK/STAT works with the epidermal growth factor receptor (EGFR) pathway to express the T-box transcription factor midline (mid). Although MID is necessary for establishing the posterior fate of the egg chamber, we show that it is not sufficient to determine a posterior fate. The ETS-transcription factor pointed (pnt) is expressed in an overlapping domain to mid in the follicle cells. This study shows that pnt is upstream of mid and that it is sufficient to induce a posterior fate in the anterior end, which is characterized by the induction of mid, the prevention of the stretched cells formation and the abrogation of border cell migration. We demonstrate that the anterior BMP signaling is abolished by PNT through dpp repression. However, ectopic DPP cannot rescue the anterior fate formation, suggesting additional targets of PNT participate in the posterior fate determination.

Fusion of the ets Transcription Factor TEL to Jak2 Results in Constitutive Jak-Stat Signaling

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4354-4364 ◽  
Author(s):  
Jen M.-Y. Ho ◽  
Bryan K. Beattie ◽  
Jeremy A. Squire ◽  
David A. Frank ◽  
Dwayne L. Barber
Keyword(s):  
Transcription Factor ◽  
Fusion Protein ◽  
Janus Kinase ◽  
Chimeric Proteins ◽  
Mobility Shift ◽  
Specific Antibodies ◽  
Hematopoietic Cell Line ◽  
Ets Transcription Factor ◽  
Electrophoretic Mobility Shift Assays ◽  
Insight Into

Abstract To study constitutive Janus kinase signaling, chimeric proteins were generated between the pointed domain of the etstranscription factor TEL and the cytosolic tyrosine kinase Jak2. The effects of these proteins on interleukin-3 (IL-3)–dependent proliferation of the hematopoietic cell line, Ba/F3, were studied. Fusion of TEL to the functional kinase (JH1) domain of Jak2 resulted in conversion of Ba/F3 cells to factor-independence. Importantly, fusion of TEL to the Jak2 pseudokinase (JH2) domain or a kinase-inactive Jak2 JH1 domain had no effect on IL-3–dependent proliferation of Ba/F3 cells. Active TEL-Jak2 constructs (consisting of either Jak2 JH1 or Jak2 JH2+JH1 domain fusions) were constitutively tyrosine-phosphorylated but did not affect phosphorylation of endogeneous Jak1, Jak2, or Jak3. TEL-Jak2 activation resulted in the constitutive tyrosine phosphorylation of Stat1, Stat3, and Stat5 as determined by detection of phosphorylation using activation-specific antibodies and by binding of each protein to a preferential GAS sequence in electrophoretic mobility shift assays. Elucidation of signaling events downstream of TEL-Jak2 activation may provide insight into the mechanism of leukemogenesis mediated by this oncogenic fusion protein.

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.

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 Septate junction proteins are required for egg elongation and border cell migration during oogenesis in Drosophila

2020 ◽  
Author(s):  
Haifa Alhadyian ◽  
Dania Shoiab ◽  
Robert E. Ward
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Migration ◽  
Developmental Stages ◽  
Septate Junction ◽  
Follicle Cells ◽  
Follicular Epithelium ◽  
Essential Requirement ◽  
Border Cell ◽  
Border Cell Migration ◽  
Protein Components

AbstractProtein components of the invertebrate occluding junction - known as the septate junction (SJ) - are required for morphogenetic developmental events during embryogenesis in Drosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell migration. We found that all four SJ proteins are expressed in the egg throughout oogenesis, with the highest and most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 10b. SJ protein relocalization requires the expression of other SJ proteins, as well as rab5 and rab11 in a manner similar to SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the border cell cluster results in border cell migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggests that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages.Article SummarySeptate junction (SJ) proteins are essential for forming an occluding junction in epithelial tissues of Drosophila melanogaster. SJ proteins are also required for morphogenetic events during embryogenesis prior to the formation of an occluding junction. To determine if SJ proteins function in morphogenesis at other developmental stages, we examined their function during oogenesis, and found that SJ proteins are expressed in the follicular epithelium of the egg chamber and are required for egg elongation, dorsal appendages formation, and border cell migration. Additionally, we found that the formation of SJs in oogenesis is similar to that in embryonic epithelia.

Fusion of the ets Transcription Factor TEL to Jak2 Results in Constitutive Jak-Stat Signaling

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4354-4364 ◽  
Author(s):  
Jen M.-Y. Ho ◽  
Bryan K. Beattie ◽  
Jeremy A. Squire ◽  
David A. Frank ◽  
Dwayne L. Barber
Keyword(s):  
Transcription Factor ◽  
Fusion Protein ◽  
Janus Kinase ◽  
Chimeric Proteins ◽  
Mobility Shift ◽  
Specific Antibodies ◽  
Hematopoietic Cell Line ◽  
Ets Transcription Factor ◽  
Electrophoretic Mobility Shift Assays ◽  
Insight Into

To study constitutive Janus kinase signaling, chimeric proteins were generated between the pointed domain of the etstranscription factor TEL and the cytosolic tyrosine kinase Jak2. The effects of these proteins on interleukin-3 (IL-3)–dependent proliferation of the hematopoietic cell line, Ba/F3, were studied. Fusion of TEL to the functional kinase (JH1) domain of Jak2 resulted in conversion of Ba/F3 cells to factor-independence. Importantly, fusion of TEL to the Jak2 pseudokinase (JH2) domain or a kinase-inactive Jak2 JH1 domain had no effect on IL-3–dependent proliferation of Ba/F3 cells. Active TEL-Jak2 constructs (consisting of either Jak2 JH1 or Jak2 JH2+JH1 domain fusions) were constitutively tyrosine-phosphorylated but did not affect phosphorylation of endogeneous Jak1, Jak2, or Jak3. TEL-Jak2 activation resulted in the constitutive tyrosine phosphorylation of Stat1, Stat3, and Stat5 as determined by detection of phosphorylation using activation-specific antibodies and by binding of each protein to a preferential GAS sequence in electrophoretic mobility shift assays. Elucidation of signaling events downstream of TEL-Jak2 activation may provide insight into the mechanism of leukemogenesis mediated by this oncogenic fusion protein.

scholarly journals Smad-Dependent Recruitment of a Histone Deacetylase/Sin3A Complex Modulates the Bone Morphogenetic Protein-Dependent Transcriptional Repressor Activity of Nkx3.2

2003 ◽  
Vol 23 (23) ◽  
pp. 8704-8717 ◽  
Author(s):  
Dae-Won Kim ◽  
Andrew B. Lassar
Keyword(s):  
Transcription Factor ◽  
Bone Morphogenetic Protein ◽  
Histone Deacetylase ◽  
Transcriptional Activation ◽  
Transcriptional Repressor ◽  
Bmp Signaling ◽  
Dependent Manner ◽  
Histone Deacetylase 1 ◽  
Morphogenetic Protein ◽  
Repressor Activity

ABSTRACT We have previously shown that Nkx3.2, a transcriptional repressor that is expressed in the sclerotome and developing cartilage, can activate the chondrocyte differentiation program in somitic mesoderm in a bone morphogenetic protein (BMP)-dependent manner. In this work, we elucidate how BMP signaling modulates the transcriptional repressor activity of Nkx3.2. We have found that Nkx3.2 forms a complex, in vivo, with histone deacetylase 1 (HDAC1) and Smad1 and -4 in a BMP-dependent manner. The homeodomain and NK domain of Nkx3.2 support the interaction of this transcription factor with HDAC1 and Smad1, respectively, and both of these domains are required for the transcriptional repressor activity of Nkx3.2. Furthermore, the recruitment of an HDAC/Sin3A complex to Nkx3.2 requires that Nkx3.2 interact with Smad1 and -4. Indeed, Nkx3.2 both fails to associate with the HDAC/Sin3A complex and represses target gene transcription in a cell line lacking Smad4, but it performs these functions if exogenous Smad4 is added to these cells. While prior work has indicated that BMP-dependent Smads can support transcriptional activation, our findings indicate that BMP-dependent Smads can also potentiate transcriptional repression, depending upon the identity of the Smad-interacting transcription factor.

Mosaic analyses reveal the function ofDrosophila Rasin embryonic dorsoventral patterning and dorsal follicle cell morphogenesis

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2209-2222 ◽  
Author(s):  
Karen E. James ◽  
Jennie B. Dorman ◽  
Celeste A. Berg
Keyword(s):  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Signal Transduction Pathway ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Follicular Epithelium ◽  
Dorsoventral Patterning ◽  
Ras Pathway ◽  
Egg Chambers ◽  
Ras Signal Transduction

In Drosophila melanogaster, the Ras signal transduction pathway is the primary effector of receptor tyrosine kinases, which govern diverse developmental programs. During oogenesis, epidermal growth factor receptor signaling through the Ras pathway patterns the somatic follicular epithelium, establishing the dorsoventral asymmetry of eggshell and embryo. Analysis of follicle cell clones homozygous for a null allele of Ras demonstrates that Ras is required cell-autonomously to repress pipe transcription, the critical first step in embryonic dorsoventral patterning. The effects of aberrant pipe expression in Ras mosaic egg chambers can be ameliorated, however, by post-pipe patterning events, which salvage normal dorsoventral polarity in most embryos derived from egg chambers with dorsal Ras clones. The patterned follicular epithelium also determines the final shape of the eggshell, including the dorsal respiratory appendages, which are formed by the migration of two dorsolateral follicle cell populations. Confocal analyses of mosaic egg chambers demonstrate that Ras is required both cell- and non cell-autonomously for morphogenetic behaviors characteristic of dorsal follicle cell migration, and reveal a novel, Ras-dependent pattern of basal E-cadherin localization in dorsal midline follicle cells.

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.

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