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.

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.

scholarly journals The Transcriptional Repressor Orphan Nuclear Receptor TLX Is Responsive to Caffeine and Istradefylline

2021 ◽  
Author(s):  
Giuseppe Faudone ◽  
Whitney Kilu ◽  
Xiaomin Ni ◽  
Apirat Chaikuad ◽  
Sridhar Sreeramulu ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Drug Target ◽  
Protein Complexes ◽  
Orphan Nuclear Receptor ◽  
Essential Factor ◽  
Stem Cell Survival ◽  
Functional Understanding ◽  
Repressor Activity

The orphan nuclear receptor TLX is expressed almost exclusively in neural stem cells. TLX acts as an essential factor for neural stem cell survival and is hence considered as a promising drug target in neurodegeneration. However, few studies have characterized the roles of TLX due to a lack of ligands and limited functional understanding. Here, we identify caffeine and istradefylline as TLX ligands that counteract the receptor’s intrinsic repressor activity in reporter gene assays and modulate TLX regulated SIRT1 and p21 expression. Mutagenesis of residues lining a cavity within the TLX ligand binding domain altered activity of these ligands suggesting direct interactions with helix 5. Using istradefylline as a tool compound, we observed ligand-sensitive recruitment of the co-repressor SMRT and heterodimerization of TLX with RXR. Both protein-protein complexes evolve as factors that modulate TLX function and suggest an unprecedented role of TLX in directly repressing other nuclear receptors.

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 Acetylation in Nuclear Receptor Signaling and the Role of Sirtuins

2008 ◽  
Vol 22 (3) ◽  
pp. 539-545 ◽  
Author(s):  
Chenguang Wang ◽  
Michael J. Powell ◽  
Vladimir M. Popov ◽  
Richard G. Pestell
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Histone Deacetylases ◽  
Receptor Activity ◽  
Receptor Signaling ◽  
Therapeutic Implications ◽  
Proline Isomerization ◽  
Receptor Complexes ◽  
Nuclear Receptor Coregulators ◽  
Coregulatory Proteins

Abstract It has been known since the early 1970s that nuclear receptor complexes bind DNA in association with coregulatory proteins. Characterization of these nuclear receptor coregulators has revealed diverse enzymatic activities that temporally and spatially coordinate nuclear receptor activity within the context of local chromatin in response to diverse hormone signals. Chromatin-modifying proteins, which dictate the higher-order chromatin structure in which DNA is packaged, in turn orchestrate orderly recruitment of nuclear receptor complexes. Modifications of histones include acetylation, methylation, phosphorylation, ubiquitylation, sumoylation, ADP ribosylation, deimination, and proline isomerization. At this time, we understand how a subset of these modifications regulates nuclear receptor signaling. However, the effects, particularly of acetylation and demethylation, are profound. The finding that nuclear receptors are directly acetylated and that acetylation in turn directly regulates contact-independent growth has broad therapeutic implications. Studies over the past 7 yr have led to the understanding that nuclear receptor acetylation is a conserved function, regulating diverse nuclear receptor activity. Furthermore, we now know that acetylation of multiple and distinct substrates within nuclear receptor signaling pathways, form an acetylation signaling network from the cell surface to the nucleus. The finding that nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases, the sirtuins, are capable of deacetylating nuclear receptors provides a new level of complexity in the control of nuclear receptor activity in which local intracellular concentrations of NAD may regulate nuclear receptor physiology.

Identification of novel genes and pathways regulated by the orphan nuclear receptor COUP-TFII in mouse MA-10 Leydig cells†

2021 ◽  
Author(s):  
Samir Mehanovic ◽  
Raifish E Mendoza-Villarroel ◽  
Karine Mattos ◽  
Philippe Talbot ◽  
Robert S Viger ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Differentially Expressed Genes ◽  
Nuclear Receptor ◽  
Leydig Cells ◽  
Target Genes ◽  
Sex Differentiation ◽  
Gonad Development ◽  
Differentially Expressed ◽  
Gene Promoters ◽  
Orphan Nuclear Receptor

Abstract In males, Leydig cells are the main producers of testosterone and insulin-like 3 (INSL3), two hormones essential for sex differentiation and reproductive functions. Chicken ovalbumin upstream promoter-transcription factors I (COUP-TFI/NR2F1) and COUP-TFII (NR2F2) belong to the steroid/thyroid hormone nuclear receptor superfamily of transcription factors. In the testis, COUP-TFII is expressed and plays a role in the differentiation of cells committed to give rise to fully functional steroidogenic adult Leydig cells. Steroid production has also been shown to be diminished in COUP-TFII-depleted Leydig cells, indicating an important functional role in steroidogenesis. Until now, only a handful of target genes have been identified for COUP-TFII in Leydig cells. To provide new information into the mechanism of action of COUP-TFII in Leydig cells, we performed microarray analyses of COUP-TFII-depleted MA-10 Leydig cells. We identified 262 differentially expressed genes in COUP-TFII-depleted MA-10 cells. Many of the differentially expressed genes are known to be involved in lipid biosynthesis, lipid metabolism, male gonad development, and steroidogenesis. We validated the microarray data for a subset of the modulated genes by RT-qPCR. Downregulated genes included Hsd3b1, Cyp11a1, Prlr, Shp/Nr0b2, Fdx1, Scarb1, Inha and Gsta3. Finally, analysis of the Gsta3 and Inha gene promoters showed that at least two of the downregulated genes are potentially new direct targets for COUP-TFII. These data provide new evidence that further strengthens the important nature of COUP-TFII in steroidogenesis, androgen homeostasis, cellular defense, and differentiation in mouse Leydig cells.

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