scholarly journals A new experimental model for the investigation of sequential hermaphroditism

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Goikoetxea ◽  
S. Muncaster ◽  
E. V. Todd ◽  
P. M. Lokman ◽  
H. A. Robertson ◽  
...  

AbstractThe stunning sexual transformation commonly triggered by age, size or social context in some fishes is one of the best examples of phenotypic plasticity thus far described. To date our understanding of this process is dominated by studies on a handful of subtropical and tropical teleosts, often in wild settings. Here we have established the protogynous New Zealand spotty wrasse, Notolabruscelidotus, as a temperate model for the experimental investigation of sex change. Captive fish were induced to change sex using aromatase inhibition or manipulation of social groups. Complete female-to-male transition occurred over 60 days in both cases and time-series sampling was used to quantify changes in hormone production, gene expression and gonadal cellular anatomy. Early-stage decreases in plasma 17β-estradiol (E2) concentrations or gonadal aromatase (cyp19a1a) expression were not detected in spotty wrasse, despite these being commonly associated with the onset of sex change in subtropical and tropical protogynous (female-to-male) hermaphrodites. In contrast, expression of the masculinising factor amh (anti-Müllerian hormone) increased during early sex change, implying a potential role as a proximate trigger for masculinisation. Collectively, these data provide a foundation for the spotty wrasse as a temperate teleost model to study sex change and cell fate in vertebrates.

Author(s):  
A Goikoetxea ◽  
S Muncaster ◽  
EV Todd ◽  
PM Lokman ◽  
H Robertson ◽  
...  

AbstractMany studies of vertebrate sex change focus on subtropical and tropical teleosts. This study presents the protogynous New Zealand spotty wrasse, Notolabrus celidotus, as a temperate model. Captive fish were induced to change sex using either aromatase inhibition or manipulation of social groups. The endocrine and genetic cascade underlying this process was investigated using time-series sampling coupled with histological staging, sex steroid quantification and nanoString nCounter mRNA analysis. Seasonality affected sex ratios and sex steroid profiles; the likelihood of sex change increased when social manipulations were performed outside of the breeding season. Early-stage decreases in plasma 17β-estradiol (E2) concentrations or gonadal aromatase (cyp19a1a) expression were not detected in spotty wrasse, despite these being associated with the onset of sex change in many protogynous hermaphrodites. Gonadal expression of 21 candidate genes was examined in relation to gonadal histology and sex steroid concentrations across sex change. When compared to other species, some genes previously implicated in sex determination and differentiation showed typical sex-specific gonadal expression patterns (foxl1, dmrt1, amh), while other critical male- and female-pathway genes exhibited unexpected patterns (cyp19a1a, rspo1, sox9a). Moreover, expression of the masculinising factor amh (anti-Müllerian hormone) increased during early sex change, implying a potential role as a proximate trigger for sex change. Dynamic expression of DNA methyltransferase genes suggested a key role of epigenetic regulation during the ovary-to-testis transformation in this species. Collectively, these data provide a foundation for the spotty wrasse as a new teleost model to study sex change and cell fate in vertebrates.


Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3295-3309 ◽  
Author(s):  
Boris Egger ◽  
Ronny Leemans ◽  
Thomas Loop ◽  
Lars Kammermeier ◽  
Yun Fan ◽  
...  

In Drosophila, the glial cells missing (gcm) gene encodes a transcription factor that controls the determination of glial versus neuronal fate. In gcm mutants, presumptive glial cells are transformed into neurons and, conversely, when gcm is ectopically misexpressed, presumptive neurons become glia. Although gcm is thought to initiate glial cell development through its action on downstream genes that execute the glial differentiation program, little is known about the identity of these genes. To identify gcm downstream genes in a comprehensive manner, we used genome-wide oligonucleotide arrays to analyze differential gene expression in wild-type embryos versus embryos in which gcm is misexpressed throughout the neuroectoderm. Transcripts were analyzed at two defined temporal windows during embryogenesis. During the first period of initial gcm action on determination of glial cell precursors, over 400 genes were differentially regulated. Among these are numerous genes that encode other transcription factors, which underscores the master regulatory role of gcm in gliogenesis. During a second later period, when glial cells had already differentiated, over 1200 genes were differentially regulated. Most of these genes, including many genes for chromatin remodeling factors and cell cycle regulators, were not differentially expressed at the early stage, indicating that the genetic control of glial fate determination is largely different from that involved in maintenance of differentiated cells. At both stages, glial-specific genes were upregulated and neuron-specific genes were downregulated, supporting a model whereby gcm promotes glial development by activating glial genes, while simultaneously repressing neuronal genes. In addition, at both stages, numerous genes that were not previously known to be involved in glial development were differentially regulated and, thus, identified as potential new downstream targets of gcm. For a subset of the differentially regulated genes, tissue-specific in vivo expression data were obtained that confirmed the transcript profiling results. This first genome-wide analysis of gene expression events downstream of a key developmental transcription factor presents a novel level of insight into the repertoire of genes that initiate and maintain cell fate choices in CNS development.


2014 ◽  
Author(s):  
Max V Staller ◽  
Charless C Fowlkes ◽  
Meghan D.J. Bragdon ◽  
Zeba B. Wunderlich ◽  
Angela DePace

In developing embryos, gene regulatory networks canalize cells towards discrete terminal fates. We studied the behavior of the anterior-posterior segmentation network in Drosophila melanogaster embryos depleted of a key maternal input, bicoid (bcd), by building a cellular- resolution gene expression atlas containing measurements of 12 core patterning genes over 6 time points in early development. With this atlas, we determine the precise perturbation each cell experiences, relative to wild type, and observe how these cells assume cell fates in the perturbed embryo. The first zygotic layer of the network, consisting of the gap and terminal genes, is highly robust to perturbation: all combinations of transcription factor expression found in bcd depleted embryos were also found in wild type embryos, suggesting that no new cell fates were created even at this very early stage. All of the gap gene expression patterns in the trunk expand by different amounts, a feature that we were unable to explain using two simple models of the effect of bcd depletion. In the second layer of the network, depletion of bcd led to an excess of cells expressing both even skipped and fushi tarazu early in the blastoderm stage, but by gastrulation this overlap resolved into mutually exclusive stripes. Thus, following depletion of bcd, individual cells rapidly canalize towards normal cell fates in both layers of this gene regulatory network. Our gene expression atlas provides a high resolution picture of a classic perturbation and will enable further modeling of canalization in this transcriptional network.


2020 ◽  
Vol 20 ◽  
Author(s):  
Helen Shiphrah Vethakanraj ◽  
Niveditha Chandrasekaran ◽  
Ashok Kumar Sekar

: Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway hydrolyzes pro-apoptotic ceramide to sphingosine, which by the action of sphingosine-1-kinase is metabolized to mitogenic sphingosine-1-phosphate. The intracellular level of AC determines ceramide/sphingosine-1-phosphate rheostat which in turn decides the cell fate. The upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased and on the other end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition, cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance, radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy thereby promoting cell death. The core objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various cancer cell lines/models.


2019 ◽  
Vol 21 (9) ◽  
pp. 631-645 ◽  
Author(s):  
Saeed Ahmed ◽  
Muhammad Kabir ◽  
Zakir Ali ◽  
Muhammad Arif ◽  
Farman Ali ◽  
...  

Aim and Objective: Cancer is a dangerous disease worldwide, caused by somatic mutations in the genome. Diagnosis of this deadly disease at an early stage is exceptionally new clinical application of microarray data. In DNA microarray technology, gene expression data have a high dimension with small sample size. Therefore, the development of efficient and robust feature selection methods is indispensable that identify a small set of genes to achieve better classification performance. Materials and Methods: In this study, we developed a hybrid feature selection method that integrates correlation-based feature selection (CFS) and Multi-Objective Evolutionary Algorithm (MOEA) approaches which select the highly informative genes. The hybrid model with Redial base function neural network (RBFNN) classifier has been evaluated on 11 benchmark gene expression datasets by employing a 10-fold cross-validation test. Results: The experimental results are compared with seven conventional-based feature selection and other methods in the literature, which shows that our approach owned the obvious merits in the aspect of classification accuracy ratio and some genes selected by extensive comparing with other methods. Conclusion: Our proposed CFS-MOEA algorithm attained up to 100% classification accuracy for six out of eleven datasets with a minimal sized predictive gene subset.


Author(s):  
Francesca Pagani ◽  
Elisa Tratta ◽  
Patrizia Dell’Era ◽  
Manuela Cominelli ◽  
Pietro Luigi Poliani

AbstractEarly B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.


Author(s):  
Guo‐Tzau Wang ◽  
He‐Yen Pan ◽  
Wei‐Han Lang ◽  
Yuan‐Ding Yu ◽  
Chang‐Huain Hsieh ◽  
...  

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Guanying Gao ◽  
Ruiqi Wu ◽  
Rongge Liu ◽  
Jianquan Wang ◽  
Yingfang Ao ◽  
...  

Abstract Background Recent studies have shown high expression levels of certain inflammatory, anabolic, and catabolic genes in the articular cartilage from the impingement zone of the hips with femoroacetabular impingement (FAI), representing an increased metabolic state. Nevertheless, little is known about the molecular properties of bone tissue from the impingement zone of hips with FAI. Methods Bone tissue samples from patients with early-stage cam-type FAI were collected during hip arthroscopy for treatment of cam-type FAI. Control bone tissue samples were collected from six patients who underwent total hip replacement because of a femoral neck fracture. Quantitative real-time polymerase chain reaction (PCR) was performed to determine the gene expression associated with inflammation and bone remodeling. The differences in the gene expression in bone tissues from the patients with early-stage cam-type FAI were also evaluated based on clinical parameters. Results In all, 12 patients with early-stage cam-type FAI and six patients in the control group were included in this study. Compared to the control samples, the bone tissue samples from patients with FAI showed higher expression levels of interleukin-6 (IL-6), alkaline phosphatase (ALP), receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) (P < 0.05). IL-1 expression was detected only in the control group. On the other hand, there was no significant difference in IL-8 expression between the patients with FAI and the control group. The patients with FAI having a body mass index (BMI) of >24 kg/m2 showed higher ALP expression (P < 0.05). Further, the expression of IL-6 and ALP was higher in the patients with FAI in whom the lateral center-edge angle was >30° (P < 0.05). Conclusions Our results indicated the metabolic condition of bone tissues in patients with early-stage cam-type FAI differed from that of normal bone in the femoral head-neck junction. The expression levels of the genes associated with inflammation and bone remodeling were higher in the bone tissue of patients with early-stage cam-type FAI than in the patients with normal bone tissue.


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