hedgehog is required for the proliferation and specification of ovarian somatic cells prior to egg chamber formation in Drosophila

Development ◽  
1996 ◽  
Vol 122 (4) ◽  
pp. 1125-1135 ◽  
Author(s):  
A.J. Forbes ◽  
H. Lin ◽  
P.W. Ingham ◽  
A.C. Spradling
Keyword(s):  
Cell Proliferation ◽  
Somatic Cells ◽  
Follicle Cells ◽  
Cell Identity ◽  
Neurogenic Genes ◽  
Terminal Filament ◽  
Hh Signaling ◽  
Egg Chamber

The hedgehog (hh) gene plays a role in regulating cell proliferation and specifying cell identity in diverse systems. We show that hh is expressed at the extreme apical end of Drosophila ovarioles in terminal filament cells and a newly identified group of associated somatic cells. Reducing or ectopically expressing hh affects somatic cells in region 2 of the germarium, 2–5 cells away from the cells in which Hh protein is detected. hh activity stimulates the proliferation of pre-follicle somatic cells, and promotes the specification of polar follicle cells. hh signaling during egg chamber assembly appears to be closely related to, or part of pathways involving the neurogenic genes.

Regulation of cell proliferation and patterning in Drosophila oogenesis by Hedgehog signaling

Development ◽  
2000 ◽  
Vol 127 (10) ◽  
pp. 2165-2176 ◽  
Author(s):  
Y. Zhang ◽  
D. Kalderon
Keyword(s):  
Hedgehog Signaling ◽  
Developmental Stages ◽  
Somatic Cells ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Cell Lineages ◽  
Egg Chambers ◽  
Hh Signaling ◽  
Egg Chamber ◽  
Activity Loss

The localized expression of Hedgehog (Hh) at the extreme anterior of Drosophila ovarioles suggests that it might provide an asymmetric cue that patterns developing egg chambers along the anteroposterior axis. Ectopic or excessive Hh signaling disrupts egg chamber patterning dramatically through primary effects at two developmental stages. First, excess Hh signaling in somatic stem cells stimulates somatic cell over-proliferation. This likely disrupts the earliest interactions between somatic and germline cells and may account for the frequent mis-positioning of oocytes within egg chambers. Second, the initiation of the developmental programs of follicle cell lineages appears to be delayed by ectopic Hh signaling. This may account for the formation of ectopic polar cells, the extended proliferation of follicle cells and the defective differentiation of posterior follicle cells, which, in turn, disrupts polarity within the oocyte. Somatic cells in the ovary cannot proliferate normally in the absence of Hh or Smoothened activity. Loss of protein kinase A activity restores the proliferation of somatic cells in the absence of Hh activity and allows the formation of normally patterned ovarioles. Hence, localized Hh is not essential to direct egg chamber patterning.

scholarly journals Orphan nuclear receptor ftz-f1 (NR5A3) promotes egg chamber survival in the Drosophila ovary

2021 ◽  
Author(s):  
Allison N Beachum ◽  
Kaitlin M Whitehead ◽  
Samantha I McDonald ◽  
Daniel N Phipps ◽  
Hanna E Berghout ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Somatic Cells ◽  
Gonad Development ◽  
Mitotic Cell ◽  
Follicle Cells ◽  
Orphan Nuclear Receptor ◽  
Receptor Signaling ◽  
Germline Stem Cells ◽  
Egg Chamber

Abstract Gamete production in mammals and insects is controlled by cell signaling pathways that facilitate communication between germ cells and somatic cells. Nuclear receptor signaling is a key mediator of many aspects of reproduction, including gametogenesis. For example, the NR5A sub-family of nuclear receptors are essential for gonad development and sex steroid production in mammals. Despite the original identification of the NR5A sub-family in the model insect Drosophila melanogaster, it has been unclear whether Drosophila NR5A receptors directly control oocyte production. Ftz-f1 is expressed throughout the ovary, including in germline stem cells, germline cysts, and several populations of somatic cells. We demonstrate that ftz-f1 is required in follicle cells prior to stage 10 to promote egg chamber survival at the mid-oogenesis checkpoint. Our data suggest that egg chamber death in the absence of ftz-f1 is due, at least in part, to failure of follicle cells to exit the mitotic cell cycle or failure to accumulate oocyte-specific factors in the germline. Taken together, these results demonstrate that, as in mammals, the NR5A sub-family promotes maximal reproductive output in Drosophila. Our data underscore the importance of nuclear receptors in the control of reproduction and highlight the utility of Drosophila oogenesis as a key model for unraveling the complexity of nuclear receptor signaling in gametogenesis.

scholarly journals miR-636 inhibits EMT, cell proliferation and cell cycle of ovarian cancer by directly targeting transcription factor Gli2 involved in Hedgehog pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiong Ma ◽  
Chunxia Zhou ◽  
Xuejun Chen
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Luciferase Reporter ◽  
Cell Proliferation And Migration ◽  
Hh Signaling ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Hedgehog (Hh) signaling pathway, which is essential for cell proliferation and differentiation, is noted to be aberrantly activated in tumor from increasing studies in recent years. MicroRNAs (miRNAs) as an important non-coding RNA in cells have been proven to possess a regulatory role specific to the Hh signaling pathway. Here, in vitro and in vivo cellular/molecular experiments were adopted to clarify the regulatory mechanism linking miR-636 to the Hh signaling pathway in ovarian cancer (OVC). Methods Protein–protein interaction analysis was performed to identify the hub gene in the Hh pathway. TargetScan database was used to predict the potential upstream regulators for Gli2. qRT-PCR was performed to test the expression of miR-636, while Western blot was conducted to detect the expression of proteins related to the Hh pathway and epithelial-mesenchymal transition (EMT). For cell functional experiments, HO-8910PM OVC cell line was used. MTT assay and wound healing assay were used to measure the effect of miR-636 on cell proliferation and migration. Flow cytometry was carried out to examine the effect of miR-636 on cell cycle, and Western blot was used to identify the change in expression of Hh and EMT-related proteins. Dual-luciferase reporter gene assay was implemented to detect the targeting relationship between miR-636 and Gli2. Xenotransplantation models were established for in vivo examination. Results Gli2 was identified as the hub gene of the Hh pathway and it was validated to be regulated by miR-636 based on the data from TargetScan and GEO databases. In vitro experiments discovered that miR-636 was significantly lowly expressed in OVC cell lines, and overexpressing miR-636 significantly inhibited HO-8910PM cell proliferation, migration and induced cell cycle arrest in G0/G1 phase, while the inhibition of miR-636 caused opposite results. Dual-luciferase reporter gene assay revealed that Gli2 was the target gene of miR-636 in OVC. Besides, overexpressed miR-636 decreased protein expression of Gli2, and affected the expression of proteins related to the Hh signaling pathway and EMT. Rescue experiments verified that overexpression of Gli2 reversed the inhibitory effect of miR-636 on HO-8910PM cell proliferation and migration, and attenuated the blocking effect of miR-636 on cell cycle. The xenotransplantation experiment suggested that miR-636 inhibited cell growth of OVC by decreasing Gli2 expression. Besides, overexpressing Gli2 potentiated the EMT process of OVC cells via decreasing E-cadherin protein expression and increasing Vimentin protein expression, and it reversed the inhibitory effect of miR-636 on OVC cell proliferation in vivo. Conclusion miR-636 mediates the activation of the Hh pathway via binding to Gli2, thus inhibiting EMT, suppressing cell proliferation and migration of OVC. Trial registration: The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of The Second Affiliated hospital of Zhejiang University School of Medicine (IR2019001235). Written informed consent was obtained from individual or guardian participants.

scholarly journals Müllerian Inhibiting Substance Is Required for Germ Cell Proliferation during Early Gonadal Differentiation in Medaka (Oryzias latipes)

Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1813-1819 ◽  
Author(s):  
Eri Shiraishi ◽  
Norifumi Yoshinaga ◽  
Takeshi Miura ◽  
Hayato Yokoi ◽  
Yuko Wakamatsu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Germ Cells ◽  
Sex Differentiation ◽  
Somatic Cells ◽  
Oryzias Latipes ◽  
Cell Number ◽  
Gonadal Differentiation ◽  
Loss Of Function ◽  
Germ Cell Proliferation

Müllerian inhibiting substance (MIS) is a glycoprotein belonging to the TGF-β superfamily. In mammals, MIS is responsible for the regression of Müllerian ducts in the male fetus. However, the role of MIS in gonadal sex differentiation of teleost fish, which have no Müllerian ducts, has yet to be clarified. In the present study, we examined the expression pattern of mis and mis type 2 receptor (misr2) mRNAs and the function of MIS signaling in early gonadal differentiation in medaka (teleost, Oryzias latipes). In situ hybridization showed that both mis and misr2 mRNAs were expressed in the somatic cells surrounding the germ cells of both sexes during early sex differentiation. Loss-of-function of either MIS or MIS type II receptor (MISRII) in medaka resulted in suppression of germ cell proliferation during sex differentiation. These results were supported by cell proliferation assay using 5-bromo-2′-deoxyuridine labeling analysis. Treatment of tissue fragments containing germ cells with recombinant eel MIS significantly induced germ cell proliferation in both sexes compared with the untreated control. On the other hand, culture of tissue fragments from the MIS- or MISRII-defective embryos inhibited proliferation of germ cells in both sexes. Moreover, treatment with recombinant eel MIS in the MIS-defective embryos dose-dependently increased germ cell number in both sexes, whereas in the MISRII-defective embryos, it did not permit proliferation of germ cells. These results suggest that in medaka, MIS indirectly stimulates germ cell proliferation through MISRII, expressed in the somatic cells immediately after they reach the gonadal primordium.

The TGF-beta signaling pathway is essential for Drosophila oogenesis

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1555-1565 ◽  
Author(s):  
V. Twombly ◽  
R.K. Blackman ◽  
H. Jin ◽  
J.M. Graff ◽  
R.W. Padgett ◽  
...  
Keyword(s):  
Family Member ◽  
Signaling Pathway ◽  
Expression Pattern ◽  
Nurse Cell ◽  
Follicle Cells ◽  
Tgf Beta ◽  
Drosophila Oogenesis ◽  
Egg Chamber

We examine roles of signaling by secreted ligands of the TGF-beta family during Drosophila oogenesis. One family member, the DPP ligand encoded by the decapentaplegic (dpp) gene, is required for patterning of anterior eggshell structures. This requirement presumably reflects the expression pattern of dpp in an anterior subset of somatic follicle cells: the centripetally migrating and the nurse cell-associated follicle cells. Similar requirements are also revealed by mutations in the saxophone (sax)-encoded receptor, consistent with the idea that DPP signaling is, at least in part, mediated by the SAX receptor. A loss of germline sax function results in a block in oogenesis associated with egg chamber degeneration and a failure of the transfer of nurse cell contents to the oocyte, indicating that TGF-beta signaling is required for these events. Some phenotypes of sax mutations during oogenesis suggest that SAX responds to at least one other TGF-beta ligand as well in the posterior follicle cells.

Influence of transforming growth factor beta1 (TGF-beta1) on the behaviour of porcine thyroid epithelial cells in primary culture through thrombospondin-1 synthesis

1999 ◽  
Vol 112 (9) ◽  
pp. 1405-1416
Author(s):  
D. Claisse ◽  
I. Martiny ◽  
B. Chaqour ◽  
Y. Wegrowski ◽  
E. Petitfrere ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Follicle Cells ◽  
Dependent Manner ◽  
Transforming Growth Factor Beta1 ◽  
Thyroid Cells ◽  
Amino Terminal ◽  
Thrombospondin 1 ◽  
Inhibitor Of Protein Synthesis

Transforming growth factor beta1 (TGF-beta1) is a secreted polypeptide that is thought to play a major role in the regulation of folliculogenesis and differentiation of thyroid cells. On porcine thyroid follicular cells cultured on plastic substratum, TGF-beta1, in a concentration-dependent way, promoted the disruption of follicles, cell spreading, migration and confluency by a mechanism that did not involve cell proliferation. TGF-beta1 strongly activated the production of thrombospondin-1 and (alpha)vbeta3 integrin in a concentration-dependent manner whereas the expression of thyroglobulin was unaffected. Anisomycin, an inhibitor of protein synthesis, inhibited the effect of TGF-beta1 on cell organization. Thrombospondin-1 reproduced the effect of TGF-beta1. In the presence of thrombospondin-1 cells did not organize in follicle-like structures but, in contrast, spreaded and reached confluency independently of cell proliferation. This effect is suppressed by an RGD-containing peptide. The adhesive properties of thrombospondin-1 for thyroid cells were shown to be mediated by both the amino-terminal heparin-binding domain and the RGD domain of thrombospondin-1. Adhesion was shown to involve (alpha)vbeta3 integrin. The results show that TGF-beta1 exerted an influence upon function and behaviour of follicle cells partly mediated by the synthesis of thrombospondin-1 and of its receptor (alpha)vbeta3 integrin.

scholarly journals Testicular Somatic Cells, not Gonocytes, Are the Major Source of Functional Activin A during Testis Morphogenesis

Endocrinology ◽  
2011 ◽  
Vol 152 (11) ◽  
pp. 4358-4367 ◽  
Author(s):  
Denise R. Archambeault ◽  
Jessica Tomaszewski ◽  
Andrew J. Childs ◽  
Richard A. Anderson ◽  
Humphrey Hung-Chang Yao
Keyword(s):  
Cell Proliferation ◽  
Sertoli Cell ◽  
Somatic Cells ◽  
Activin A ◽  
Protein Product ◽  
Conditional Knockout ◽  
Seminiferous Tubules ◽  
Testis Size ◽  
Testis Development ◽  
Testis Cord

Proper development of the seminiferous tubules (or testis cords in embryos) is critical for male fertility. Sertoli cells, somatic components of the seminiferous tubules, serve as nurse cells to the male germline, and thus their numbers decide the quantity of sperm output in adulthood. We previously identified activin A, the protein product of the activin βA (Inhba) gene, as a key regulator of murine Sertoli cell proliferation and testis cord expansion during embryogenesis. Although our genetic studies implicated fetal Leydig cells as the primary producers of testicular activin A, gonocytes are another potential source. To investigate the relative contribution of gonocyte-derived activin A to testis morphogenesis, we compared testis development in the Inhba global knockout mouse, which lacks activin A production in all cells (including the gonocytes), and a steroidogenic factor 1 (Sf1)-specific conditional knockout model in which activin A expression in testicular somatic cells is disrupted but gonocyte expression of activin A remains intact. Surprisingly, testis development was comparable in these two models of activin A insufficiency, with similar reductions in Sertoli cell proliferation and minor differences in testis histology. Thus, our findings suggest activin A from male gonocytes is insufficient to promote Sertoli cell proliferation and testis cord expansion in the absence of somatic cell-derived activin A. Evaluation of adult male mice with fetal disruption of activin A revealed reduced testis size, lowered sperm production, altered testicular histology, and elevated plasma FSH levels, defects reminiscent of human cases of androgen-sufficient idiopathic oligozoospermia.

scholarly journals FGFRL1 Promotes Ovarian Cancer Progression by Crosstalk with Hedgehog Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Haiyan Tai ◽  
Zhiyong Wu ◽  
Su’an Sun ◽  
Zhigang Zhang ◽  
Congjian Xu
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Hh Signaling ◽  
And Migration

Fibroblast growth factor receptor-like-1 (FGFRL1) has been identified as the fifth fibroblast growth factor receptor. So far, little is known about its biological functions, particularly in cancer development. Here, for the first time, we demonstrated the roles of FGFRL1 in ovarian carcinoma (OC). An array and existing databases were used to investigate the expression profile of FGFRL1 and the relationship between FGFRL1 expression and clinicopathological parameters. FGFRL1 was significantly upregulated in OC patients, and high FGFRL1 expression was correlated with poor prognosis. In vitro cell proliferation, apoptosis and migration assays, and in vivo subcutaneous xenograft tumor models were used to determine the role of FGFRL1. Loss of function of FGFRL1 significantly influenced cell proliferation, apoptosis, and migration of OC cells in vitro and tumor growth in vivo. Chromatin immunoprecipitation PCR analysis and microarray hybridization were performed to uncover the mechanism. FGFRL1 expression could be induced by hypoxia through hypoxia-inducible factor 1α, which directly binds to the promoter elements of FGFRL1. FGFRL1 promoted tumor progression by crosstalk with Hedgehog (Hh) signaling. Taken together, FGFRL1 is a potential predictor and plays an important role in tumor growth and Hh signaling which could serve as potential therapeutic targets for the treatment of OC.

scholarly journals Requirement for cell-proliferation control genes in Drosophila oogenesis.

Genetics ◽  
1991 ◽  
Vol 127 (3) ◽  
pp. 525-533
Author(s):  
J Szabad ◽  
V A Jursnich ◽  
P J Bryant
Keyword(s):  
Cell Proliferation ◽  
Germ Line ◽  
Follicle Cell ◽  
Mitotic Recombination ◽  
Follicle Cells ◽  
Egg Development ◽  
Proliferation Control ◽  
Dominant Female ◽  
Female Germ Line ◽  
Cell Proliferation Control

Abstract Genes that are required for cell proliferation control in Drosophila imaginal discs were tested for function in the female germ-line and follicle cells. Chimeras and mosaics were produced in which developing oocytes and nurse cells were mutant at one of five imaginal disc overgrowth loci (fat, lgd, lgl, c43 and dco) while the enveloping follicle cells were normal. The chimeras were produced by transplantation of pole cells and the mosaics were produced by X-ray-induced mitotic recombination using the dominant female-sterile technique. The results show that each of the genes tested plays an essential role in the development or function of the female germ line. The fat, lgl and c43 homozygous germ-line clones fail to produce eggs, indicating a germ-line requirement for the corresponding genes. Perdurance of the fat+ gene product in mitotic recombination clones allows the formation of a few infertile eggs from fat homozygous germ-line cells. The lgd homozygous germ-line clones give rise to a few eggs with abnormal chorionic appendages, a defect thought to result from defective cell communication between the mutant germ-line and the nonmutant follicle cells. One allele of dco (dcole88) prevents egg development when homozygous in the germ line, whereas the dco18 allele has no effect on germ-line development. Fs(2)Ugra, a recently described follicle cell-dependent dominant female-sterile mutation, allowed the analysis of egg primordia in which fat, lgd or lgl homozygous mutant follicle cells surrounded normal oocytes. The results show that the fat and lgd genes are not required for follicle cell functions, while absence of lgl function in follicles prevents egg development.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Identification of Xenopus S6 protein kinase homologs (pp90rsk) in somatic cells: phosphorylation and activation during initiation of cell proliferation.

1990 ◽  
Vol 10 (6) ◽  
pp. 3204-3215 ◽  
Author(s):  
R H Chen ◽  
J Blenis
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Cultured Cells ◽  
Animal Cell ◽  
Somatic Cells ◽  
Cross Reactivity ◽  
S6 Kinase ◽  
Quiescent Cells ◽  
Molecular Sizes

We have identified human, mouse, and chicken homologs to Xenopus S6 protein kinase II (S6KII). In quiescent cells, the apparent molecular mass of the Xenopus homologs (referred to as pp90rsk) increased from a range of 81 to 91 to a range of 85 to 92 kilodaltons following serum addition, which is consistent with an increase in protein phosphorylation. Indeed, serum growth factors stimulated pp90rsk phosphorylation at multiple serine and threonine residues. Furthermore, pp90rsk activity was stimulated within seconds of serum addition. Distinct molecular sizes, chromatographic properties, phosphopeptide maps, and kinetics of activation, the lack of immunological cross-reactivity, and analysis of S6 kinase activities in cells that overexpressed pp90rsk suggest that pp90rsk and pp70-S6 protein kinase, a previously identified mitogen- and oncogene-regulated S6 kinase in cultured cells, are distinct and differentially regulated. The notion that both enzymes are regulated by protein phosphorylation was supported by the ability to inactivate their S6 phosphotransferase activities with potato acid phosphatase. These data demonstrate that homologs to the Xenopus S6 protein kinases are produced and regulated by protein phosphorylation in somatic cells and that, in addition to a proposed role in Xenopus oocyte maturation, these homologs may participate in the initiation of animal cell proliferation.

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