@article {121, title = {Transcriptome profile of the sinoatrial ring reveals conserved and novel genetic programs of the zebrafish pacemaker.}, journal = {BMC Genomics}, volume = {22}, year = {2021}, month = {2021 Oct 02}, pages = {715}, abstract = {

BACKGROUND: Sinoatrial Node (SAN) is part of the cardiac conduction system, which controls the rhythmic contraction of the vertebrate heart. The SAN consists of a specialized pacemaker cell population that has the potential to generate electrical impulses. Although the SAN pacemaker has been extensively studied in mammalian and teleost models, including the zebrafish, their molecular nature remains inadequately comprehended.

RESULTS: To characterize the molecular profile of the zebrafish sinoatrial ring (SAR) and elucidate the mechanism of pacemaker function, we utilized the transgenic line sqet33mi59BEt to isolate cells of the SAR of developing zebrafish embryos and profiled their transcriptome. Our analyses identified novel candidate genes and well-known conserved signaling pathways involved in pacemaker development. We show that, compared to the rest of the heart, the zebrafish SAR overexpresses several mammalian SAN pacemaker signature genes, which include hcn4 as well as those encoding calcium- and potassium-gated channels. Moreover, genes encoding components of the BMP and Wnt signaling pathways, as well as members of the Tbx family, which have previously been implicated in pacemaker development, were also overexpressed in the SAR. Among SAR-overexpressed genes, 24 had human homologues implicated in 104 different ClinVar phenotype entries related to various forms of congenital heart diseases, which suggest the relevance of our transcriptomics resource to studying human heart conditions. Finally, functional analyses of three SAR-overexpressed genes, pard6a, prom2, and atp1a1a.2, uncovered their novel role in heart development and physiology.

CONCLUSION: Our results established conserved aspects between zebrafish and mammalian pacemaker function and revealed novel factors implicated in maintaining cardiac rhythm. The transcriptome data generated in this study represents a unique and valuable resource for the study of pacemaker function and associated heart diseases.

}, keywords = {Animals, Heart Rate, Humans, Sinoatrial Node, Transcriptome, Zebrafish}, issn = {1471-2164}, doi = {10.1186/s12864-021-08016-z}, author = {Minhas, Rashid and Loeffler-Wirth, Henry and Siddiqui, Yusra H and Obr{\k e}bski, Tomasz and Vashisht, Shikha and Nahia, Karim Abu and Paterek, Alexandra and Brzozowska, Angelika and Bugajski, Lukasz and Piwocka, Katarzyna and Korzh, Vladimir and Binder, Hans and Winata, Cecilia Lanny} } @article {115, title = {Targeted RNA Knockdown by a Type III CRISPR-Cas Complex in Zebrafish.}, journal = {CRISPR J}, volume = {3}, year = {2020}, month = {2020 08}, pages = {299-313}, abstract = {

RNA interference is a powerful experimental tool for RNA knockdown, but not all organisms are amenable. Here, we provide a proof of principle demonstration that a type III Csm effector complex can be used for programmable mRNA transcript degradation in eukaryotes. In zebrafish, Csm complex (StCsm) proved effective for knockdown of maternally expressed in germ cells of fish. It also led to significant, albeit less drastic, fluorescence reduction at one day postfertilization in and ( fish that express zygotically. StCsm targeted against the endogenous elicited the characteristic one-eyed phenotype with greater than 50\% penetrance, and hence with similar efficiency to morpholino-mediated knockdown. We conclude that Csm-mediated knockdown is very efficient for maternal transcripts and can also be used for mixed maternal/early zygotic and early zygotic transcripts, in some cases reaching comparable efficiency to morpholino-based knockdown without significant off-target effects.

}, issn = {2573-1602}, doi = {10.1089/crispr.2020.0032}, author = {Fricke, Thomas and Smalakyte, Dalia and Lapinski, Maciej and Pateria, Abhishek and Weige, Charles and Pastor, Michal and Kolano, Agnieszka and Winata, Cecilia and Siksnys, Virginijus and Tamulaitis, Gintautas and Bochtler, Matthias} } @article {pmid29972882, title = {The translational regulation of maternal mRNAs in time and space}, journal = {FEBS Lett.}, year = {2018}, month = {Jul}, abstract = {

Since their discovery, the study of maternal mRNAs has led to the identification of mechanisms underlying their spatiotemporal regulation within the context of oogenesis and early embryogenesis. Following synthesis in the oocyte, maternal mRNAs are translationally silenced and sequestered into storage in cytoplasmic granules. At the same time, their unique distribution patterns throughout the oocyte and embryo are tightly controlled and connected to their functions in downstream embryonic processes. At certain points in oogenesis and early embryogenesis, maternal mRNAs are translationally activated to perform their functions in a timely manner. The cytoplasmic polyadenylation machinery is responsible for the translational activation of maternal mRNAs, and its role in initiating the maternal to zygotic transition events has recently come to light. Here, we summarize the current knowledge on maternal mRNA regulation, with particular focus on cytoplasmic polyadenylation as a mechanism for translational regulation.

}, author = {Winata, C. L. and Korzh, V.} } @article {65, title = {Transcriptome kinetics of arsenic-induced adaptive response in zebrafish liver.}, journal = {Physiol Genomics}, volume = {27}, year = {2006}, month = {2006 Nov 27}, pages = {351-61}, abstract = {

Arsenic is a prominent environmental toxicant and carcinogen; however, its molecular mechanism of toxicity and carcinogenicity remains poorly understood. In this study, we performed microarray-based expression profiling on liver of zebrafish exposed to 15 parts/million (ppm) arsenic [As(V)] for 8-96 h to identify global transcriptional changes and biological networks involved in arsenic-induced adaptive responses in vivo. We found that there was an increase of transcriptional activity associated with metabolism, especially for biosyntheses, membrane transporter activities, cytoplasm, and endoplasmic reticulum in the 96 h of arsenic treatment, while transcriptional programs for proteins in catabolism, energy derivation, and stress response remained active throughout the arsenic treatment. Many differentially expressed genes encoding proteins involved in heat shock proteins, DNA damage/repair, antioxidant activity, hypoxia induction, iron homeostasis, arsenic metabolism, and ubiquitin-dependent protein degradation were identified, suggesting strongly that DNA and protein damage as a result of arsenic metabolism and oxidative stress caused major cellular injury. These findings were comparable with those reported in mammalian systems, suggesting that the zebrafish liver coupled with the available microarray technology present an excellent in vivo toxicogenomic model for investigating arsenic toxicity. We proposed an in vivo, acute arsenic-induced adaptive response model of the zebrafish liver illustrating the relevance of many transcriptional activities that provide both global and specific information of a coordinated adaptive response to arsenic in the liver.

}, keywords = {Adaptation, Physiological, Animals, Arsenic, Down-Regulation, Gene Expression Profiling, Gene Expression Regulation, Genomics, Liver, Male, Metabolic Networks and Pathways, Oligonucleotide Array Sequence Analysis, Transcription, Genetic, Up-Regulation, Zebrafish}, issn = {1531-2267}, doi = {10.1152/physiolgenomics.00201.2005}, author = {Lam, Siew Hong and Winata, Cecilia L and Tong, Yan and Korzh, Svetlana and Lim, Wen San and Korzh, Vladimir and Spitsbergen, Jan and Mathavan, Sinnakarupan and Miller, Lance D and Liu, Edison T and Gong, Zhiyuan} }