scholarly journals Which actin genes are necessary for zebrafish heart development and function?

2020 ◽  
Author(s):  
Kendal Prill ◽  
Matiyo Ojehomon ◽  
Love Sandhu ◽  
Suchandrima Dutta ◽  
John F. Dawson

AbstractHeart failure is the number one cause of mortality in the world, contributed to by cardiovascular disease. Many diseases of the heart muscle are caused by mutations in genes encoding contractile proteins, including cardiac actin mutations. Zebrafish are an advantageous system for modeling cardiac disease since embryos can develop without a functional heart. However, genome duplication in the teleost lineage creates a unique obstacle by increasing the number of genes involved in heart development. Four actin genes are expressed in the zebrafish heart: acta1b; actc1c; and duplicates of actc1a on chromosome 19 and 20. Here, we characterize the actin genes involved in early zebrafish heart development using in situ hybridization and CRISPR targeting to determine which gene is best to model changes seen in human patients with heart disease. The actc1a and acta1b genes are predominant during embryonic heart development, resulting in severe cardiac phenotypes when targeted with CRISPRs. Targeting these two cardiac genes with CRISPRs simultaneously results in a more severe phenotype than their individual counterparts, with the results suggesting compensation for lost actin genes by other actin paralogues. Given the duplication of the actc1a gene, we recommend acta1b as the best gene for targeted cardiac actin research.

2017 ◽  
Author(s):  
Xin Sun ◽  
Swetansu K. Hota ◽  
Yu-Qing Zhou ◽  
Stefanie Novak ◽  
Dario Miguel-Perez ◽  
...  

AbstractHow gene networks controlling organ-specific properties are modulated by chromatin remodeling complexes is not well understood. Baf60c (Smarcd3) encodes a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex. Its role throughout heart development is not fully understood. We show that constitutive loss of Baf60c leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of Baf60c in cardiomyocytes results in postnatal dilated cardiomyopathy with impaired contractile function. Baf60c regulates a gene expression program that includes genes encoding contractile proteins, modulators of sarcomere function, and cardiac metabolic genes. Many of the genes deregulated in Baf60c null embryos are targets of the MEF2/SRF co-factor Myocardin (MYOCD). In a yeast two-hybrid screen we identify MYOCD as a BAF60c interacting factor; we show that BAF60c and MYOCD directly and functionally interact. We conclude that Baf60c is essential for coordinating a program of gene expression that regulates the fundamental functional properties of cardiomyocytes.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marianna Török ◽  
Petra Merkely ◽  
Anna Monori-Kiss ◽  
Eszter Mária Horváth ◽  
Réka Eszter Sziva ◽  
...  

Abstract Background We aimed to identify sex differences in the network properties and to recognize the geometric alteration effects of long-term swim training in a rat model of exercise-induced left ventricular (LV) hypertrophy. Methods Thirty-eight Wistar rats were divided into four groups: male sedentary, female sedentary, male exercised and female exercised. After training sessions, LV morphology and function were checked by echocardiography. The geometry of the left coronary artery system was analysed on pressure-perfused, microsurgically prepared resistance artery networks using in situ video microscopy. All segments over > 80 μm in diameter were studied using divided 50-μm-long cylindrical ring units of the networks. Oxidative-nitrative (O-N) stress markers, adenosine A2A and estrogen receptor (ER) were investigated by immunohistochemistry. Results The LV mass index, ejection fraction and fractional shortening significantly increased in exercised animals. We found substantial sex differences in the coronary network in the control groups and in the swim-trained animals. Ring frequency spectra were significantly different between male and female animals in both the sedentary and trained groups. The thickness of the wall was higher in males as a result of training. There were elevations in the populations of 200- and 400-μm vessel units in males; the thinner ones developed farther and the thicker ones closer to the orifice. In females, a new population of 200- to 250-μm vessels appeared unusually close to the orifice. Conclusions Physical activity and LV hypertrophy were accompanied by a remodelling of coronary resistance artery network geometry that was different in both sexes.


Plants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 113
Author(s):  
María-Dolores Rey ◽  
Carmen Ramírez ◽  
Azahara C. Martín

Polyploidization, or whole genome duplication (WGD), has an important role in evolution and speciation. One of the biggest challenges faced by a new polyploid is meiosis, in particular, discriminating between multiple related chromosomes so that only homologs recombine to ensure regular chromosome segregation and fertility. Here, we report the production of two new hybrids formed by the genomes of species from three different genera: a hybrid between Aegilops tauschii (DD), Hordeum chilense (HchHch), and Secale cereale (RR) with the haploid genomic constitution HchDR (n = 7× = 21); and a hybrid between Triticum turgidum spp. durum (AABB), H. chilense, and S. cereale with the constitution ABHchR (n = 7× = 28). We used genomic in situ hybridization and immunolocalization of key meiotic proteins to establish the chromosome composition of the new hybrids and to study their meiotic behavior. Interestingly, there were multiple chromosome associations at metaphase I in both hybrids. A high level of crossover (CO) formation was observed in HchDR, which shows the possibility of meiotic recombination between the different genomes. We succeeded in the duplication of the ABHchR genome, and several amphiploids, AABBHchHchRR, were obtained and characterized. These results indicate that recombination between the genera of three economically important crops is possible.


2020 ◽  
Vol 92 (6) ◽  
pp. 977-984
Author(s):  
Mayya V. Kulikova ◽  
Albert B. Kulikov ◽  
Alexey E. Kuz’min ◽  
Anton L. Maximov

AbstractFor previously studied Fischer–Tropsch nanosized Fe catalyst slurries, polymer compounds with or without polyconjugating structures are used as precursors to form the catalyst nanomatrix in situ, and several catalytic experiments and X-ray diffraction and atomic force microscopy measurements are performed. The important and different roles of the paraffin molecules in the slurry medium in the formation and function of composite catalysts with the two types of aforementioned polymer matrices are revealed. In the case of the polyconjugated polymers, the alkanes in the medium are “weakly” coordinated with the metal-polymer composites, which does not affect the effectiveness of the polyconjugated polymers. Otherwise, alkane molecules form a “tight” surface layer around the composite particles, which create transport complications for the reagents and products of Fischer-Tropsch synthesis and, in some cases, can change the course of the in situ catalyst formation.


Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 613-621 ◽  
Author(s):  
Douglas R Dorer ◽  
Jamie A Rudnick ◽  
Etsuko N Moriyama ◽  
Alan C Christensen

Abstract Within the unique Triplo-lethal region (Tpl) of the Drosophila melanogaster genome we have found a cluster of 20 genes encoding a novel family of proteins. This family is also present in the Anopheles gambiae genome and displays remarkable synteny and sequence conservation with the Drosophila cluster. The family is also present in the sequenced genome of D. pseudoobscura, and homologs have been found in Aedes aegypti mosquitoes and in four other insect orders, but it is not present in the sequenced genome of any noninsect species. Phylogenetic analysis suggests that the cluster evolved prior to the divergence of Drosophila and Anopheles (250 MYA) and has been highly conserved since. The ratio of synonymous to nonsynonymous substitutions and the high codon bias suggest that there has been selection on this family both for expression level and function. We hypothesize that this gene family is Tpl, name it the Osiris family, and consider possible functions. We also predict that this family of proteins, due to the unique dosage sensitivity and the lack of homologs in noninsect species, would be a good target for genetic engineering or novel insecticides.


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Peng Chen ◽  
Hongyang Jing ◽  
Mingtao Xiong ◽  
Qian Zhang ◽  
Dong Lin ◽  
...  

AbstractThe genes encoding for neuregulin1 (NRG1), a growth factor, and its receptor ErbB4 are both risk factors of major depression disorder and schizophrenia (SZ). They have been implicated in neural development and synaptic plasticity. However, exactly how NRG1 variations lead to SZ remains unclear. Indeed, NRG1 levels are increased in postmortem brain tissues of patients with brain disorders. Here, we studied the effects of high-level NRG1 on dendritic spine development and function. We showed that spine density in the prefrontal cortex and hippocampus was reduced in mice (ctoNrg1) that overexpressed NRG1 in neurons. The frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced in both brain regions of ctoNrg1 mice. High expression of NRG1 activated LIMK1 and increased cofilin phosphorylation in postsynaptic densities. Spine reduction was attenuated by inhibiting LIMK1 or blocking the NRG1–LIMK1 interaction, or by restoring NRG1 protein level. These results indicate that a normal NRG1 protein level is necessary for spine homeostasis and suggest a pathophysiological mechanism of abnormal spines in relevant brain disorders.


2020 ◽  
Vol 31 (1-2) ◽  
pp. 2-16 ◽  
Author(s):  
Nobuyo Maeda-Smithies ◽  
Sylvia Hiller ◽  
Sharlene Dong ◽  
Hyung-Suk Kim ◽  
Brian J. Bennett ◽  
...  

AbstractStabilin2 (Stab2) encodes a large transmembrane protein which is predominantly expressed in the liver sinusoidal endothelial cells (LSECs) and functions as a scavenger receptor for various macromolecules including hyaluronans (HA). In DBA/2J mice, plasma HA concentration is ten times higher than in 129S6 or C57BL/6J mice, and this phenotype is genetically linked to the Stab2 locus. Stab2 mRNA in the LSECs was significantly lower in DBA/2J than in 129S6, leading to reduced STAB2 proteins in the DBA/2J LSECs. We found a retrovirus-derived transposable element, intracisternal A particle (IAP), in the promoter region of Stab2DBA which likely interferes with normal expression in the LSECs. In contrast, in other tissues of DBA/2J mice, the IAP drives high ectopic Stab2DBA transcription starting within the 5′ long terminal repeat of IAP in a reverse orientation and continuing through the downstream Stab2DBA. Ectopic transcription requires the Stab2-IAP element but is dominantly suppressed by the presence of loci on 59.7–73.0 Mb of chromosome (Chr) 13 from C57BL/6J, while the same region in 129S6 requires additional loci for complete suppression. Chr13:59.9–73 Mb contains a large number of genes encoding Krüppel-associated box-domain zinc-finger proteins that target transposable elements-derived sequences and repress their expression. Despite the high amount of ectopic Stab2DBA transcript in tissues other than liver, STAB2 protein was undetectable and unlikely to contribute to the plasma HA levels of DBA/2J mice. Nevertheless, the IAP insertion and its effects on the transcription of the downstream Stab2DBA exemplify that stochastic evolutional events could significantly influence susceptibility to complex but common diseases.


PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0212992 ◽  
Author(s):  
Laurent Dupays ◽  
Norma Towers ◽  
Sophie Wood ◽  
Anna David ◽  
Daniel J. Stuckey ◽  
...  

2014 ◽  
Vol 81 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Bhagyalakshmi Kalidass ◽  
Muhammad Farhan Ul-Haque ◽  
Bipin S. Baral ◽  
Alan A. DiSpirito ◽  
Jeremy D. Semrau

ABSTRACTIt is well known that copper is a key factor regulating expression of the two forms of methane monooxygenase found in proteobacterial methanotrophs. Of these forms, the cytoplasmic, or soluble, methane monooxygenase (sMMO) is expressed only at low copper concentrations. The membrane-bound, or particulate, methane monooxygenase (pMMO) is constitutively expressed with respect to copper, and such expression increases with increasing copper. Recent findings have shown that copper uptake is mediated by a modified polypeptide, or chalkophore, termed methanobactin. Although methanobactin has high specificity for copper, it can bind other metals, e.g., gold. Here we show that inMethylosinus trichosporiumOB3b, sMMO is expressed and active in the presence of copper if gold is also simultaneously present. Such expression appears to be due to gold binding to methanobactin produced byM. trichosporiumOB3b, thereby limiting copper uptake. Such expression and activity, however, was significantly reduced if methanobactin preloaded with copper was also added. Further, quantitative reverse transcriptase PCR (RT-qPCR) of transcripts of genes encoding polypeptides of both forms of MMO and SDS-PAGE results indicate that both sMMO and pMMO can be expressed when copper and gold are present, as gold effectively competes with copper for binding to methanobactin. Such findings suggest that under certain geochemical conditions, both forms of MMO may be expressed and activein situ. Finally, these findings also suggest strategies whereby field sites can be manipulated to enhance sMMO expression, i.e., through the addition of a metal that can compete with copper for binding to methanobactin.


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