scholarly journals Maternal Genetic Effects in Astyanax Cavefish Development 

2018 ◽  
Vol 1 ◽  
Author(s):  
William Jeffery

The role of maternal factors in the evolution of development is poorly understood. Here we describe the use of reciprocal hybridization between the surface dwelling (surface fish, SF) and cave dwelling (cavefish, CF) morphs of the teleost Astyanax mexicanus to determine investigate the roles of maternal genetic effects in cavefish development. Reciprocal hybridization, a procedure in which F1 hybrids are generated by fertilizing SF eggs with CF sperm (SF X CF hybrids) and CF eggs with SF sperm (CF X SF hybrids), revealed that the CF degenerative eye phenotype showed maternal genetic effects. The eyes of CF X SF hybrids resembled the degenerate eyes of CF in showing ventral reduction of the retina and corresponding displacement of the lens within the optic cup, a smaller lens and eyeball, more lens apoptosis, a smaller cartilaginous sclera, and lens-specific gene expression characteristics compared to SF X CF hybrids, which showed eye and lens gene expression phenotypes resembling SF. In contrast, reciprocal hybridization failed to support any roles for maternal genetic effects in the CF regressive pigmentation phenotype or in CF constructive changes related to enhanced jaw development. The Astyanax orthologs of mMaternal transcripts encoded by some of thethe pou2f1b, runx2b, and axin1 genes, which are key involved in determining ventral embryonic fates, genes involved in zebrafish dorsoventral patterning were increased in unfertilized CF eggs. In contrast, maternal mRNAs encoded by the ß-catenin and syntabulin genes, which control dorsal embryonic fates, were unchangedwith theshowed similar expression levels in unfertilized SF and CF eggs. This study reveals that CF eye degeneration is controlled by changes in maternal factors produced during oogenesis and introduces A. mexicanus as a model system for studying the role of maternal changes in the evolution of development.

1993 ◽  
Vol 4 (6) ◽  
pp. 204-209 ◽  
Author(s):  
Wolfgang Schmid ◽  
Doris Nitsch ◽  
Michael Boshart ◽  
Günther Schütz

2018 ◽  
Vol 49 (2) ◽  
pp. 91
Author(s):  
N. G. KOSTOMITSOPOULOS (Ν.Γ. ΚΩΣΤΟΜΗΤΣΟΠΟΥΛΟΣ)

The oestrogen receptor is a ligand-activated transcription factor that modulates specific gene expression by binding to short DNA sequences. The study of the role of oestrogen receptor on the expression of the mitogenic actionof oestrogens and oncogenesis lead biomedical research in new approaches of the treatment of oestrogen-dependent tumors by using antioestrogens. Main mechanism of action of antioestrogens is the prevention of oestrogen action by blocking the binding of oestradiol to the oestrogen receptor. Tamoxifen, the most wellknown antioestrogen, is widely used as adjuvant therapy in all stages of human breast cancer. Recently interest is focused on the potential use of "pure" antioestrogens. The use of antioestrogens in veterinary oncology is also under discussion.


Blood ◽  
2019 ◽  
Vol 134 (24) ◽  
pp. 2195-2208 ◽  
Author(s):  
Daniel Sasca ◽  
Haiyang Yun ◽  
George Giotopoulos ◽  
Jakub Szybinski ◽  
Theo Evan ◽  
...  

Cohesin mutations are common in myeloid malignancy. Sasca et al elucidate the potential role of cohesin loss in myelodysplastic syndrome and acute myeloid leukemia (MDS/AML). They demonstrate that cohesin binding is critical for erythroid-specific gene expression and that reduction in cohesin impairs terminal erythroid maturation and promotes myeloid malignancy.


1998 ◽  
Vol 273 (49) ◽  
pp. 32988-32994 ◽  
Author(s):  
Guozhi Xiao ◽  
Dian Wang ◽  
M. Douglas Benson ◽  
Gerard Karsenty ◽  
Renny T. Franceschi

Author(s):  
Mario Cioce ◽  
Claudia Canino ◽  
Harvey Pass ◽  
Giovanni Blandino ◽  
Sabrina Strano ◽  
...  

Abstract Background High resistance to therapy and poor prognosis characterizes malignant pleural mesothelioma (MPM). In fact, the current lines of treatment, based on platinum and pemetrexed, have limited impact on the survival of MPM patients. Adaptive response to therapy-induced stress involves complex rearrangements of the MPM secretome, mediated by the acquisition of a senescence-associated-secretory-phenotype (SASP). This fuels the emergence of chemoresistant cell subpopulations, with specific gene expression traits and protumorigenic features. The SASP-driven rearrangement of MPM secretome takes days to weeks to occur. Thus, we have searched for early mediators of such adaptive process and focused on metabolites differentially released in mesothelioma vs mesothelial cell culture media, after treatment with pemetrexed. Methods Mass spectrometry-based (LC/MS and GC/MS) identification of extracellular metabolites and unbiased statistical analysis were performed on the spent media of mesothelial and mesothelioma cell lines, at steady state and after a pulse with pharmacologically relevant doses of the drug. ELISA based evaluation of arachidonic acid (AA) levels and enzyme inhibition assays were used to explore the role of cPLA2 in AA release and that of LOX/COX-mediated processing of AA. QRT-PCR, flow cytometry analysis of ALDH expressing cells and 3D spheroid growth assays were employed to assess the role of AA at mediating chemoresistance features of MPM. ELISA based detection of p65 and IkBalpha were used to interrogate the NFkB pathway activation in AA-treated cells. Results We first validated what is known or expected from the mechanism of action of the antifolate. Further, we found increased levels of PUFAs and, more specifically, arachidonic acid (AA), in the transformed cell lines treated with pemetrexed. We showed that pharmacologically relevant doses of AA tightly recapitulated the rearrangement of cell subpopulations and the gene expression changes happening in pemetrexed -treated cultures and related to chemoresistance. Further, we showed that release of AA following pemetrexed treatment was due to cPLA2 and that AA signaling impinged on NFkB activation and largely affected anchorage-independent, 3D growth and the resistance of the MPM 3D cultures to the drug. Conclusions AA is an early mediator of the adaptive response to pem in chemoresistant MPM and, possibly, other malignancies.


2020 ◽  
Author(s):  
Sarmistha Adhikari ◽  
PARAMITA MANDAL

Abstract ObjectivesSevere aplastic anemia is characterized by a hypocellular bone marrow and peripheral cytopenia. Mesenchymal stem cells (MSCs) play a crucial role in haematopoietic stem cells (HSCs) development and the microenvironment suitable for haematopoiesis. Investigation of the therapeutic targets by paediatric patient-specific gene expression analysis of the MSCs can be important for diagnosis.MethodsThe study was based on freely available miRNA and host gene expression in NCBI GEO dataset. Microarray based gene expression profiles (GSE33812) of MSCs for five paediatric aplastic anaemia patients and healthy controls were generated using Agilent-014850 platform and the data was downloaded from the database.ResultsMSCs gene expression profiling distinguished between healthy controls, children with aplastic anemia. Angioteninogen (AGT) gene involved in ERK1/ERK2 cascade, cyotokine secretion, metabolic processes was strongly down-regulated among all the patients with aplastic anemia. Emerging role of various transcription factors binding to this gene was identified as a new avenue of therapeutic application.ConclusionsAs a potential diagnostic tool, patient-specific gene expression profiling of MSCs made it possible to make the difficult diagnosis of most patients with aplastic anemia.


Sign in / Sign up

Export Citation Format

Share Document