Publications by authors named "Corinna Singleman"

5 Publications

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PCB and TCDD derived embryonic cardiac defects result from a novel AhR pathway.

Aquat Toxicol 2021 Apr 25;233:105794. Epub 2021 Feb 25.

Department of Biology, Queens College, City University of New York, 65-30 Kissena Blvd, Queens NY 11367-1597, USA; The Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA. Electronic address:

Polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are environmental contaminants known to impact cardiac development, a key step in the embryonic development of most animals. To date, little is understood of the molecular mechanism driving the observed cardiac defects in exposed fishes. The literature shows PCB & TCDD derived cardiac defects are concurrent with, but not caused by, expression of cyp1A, due to activation of the aryl hydrocarbon receptor (AhR) gene activation pathway. However, in this study, detailed visualization of fish hearts exposed to PCBs and TCDD show that, in addition to a failure of cardiac looping in early heart development, the inner endocardial lining of the heart fails to maintain proper cell adhesion and tissue integrity. The resulting gap between the endocardium and myocardium in both zebrafish and Atlantic sturgeon suggested functional faults in endothelial adherens junction formation. Thus, we explored the molecular mechanism triggering cardiac defects using immunohistochemistry to identify the location and phosphorylation state of key regulatory and adhesion molecules. We hypothesized that PCB and TCDD activates AhR, phosphorylating Src, which then phosphorylates the endothelial adherens junction protein, VEcadherin. When phosphorylated, VEcadherin dimers, found in the endocardium and vasculature, separate, reducing tissue integrity. In zebrafish, treatment with PCB and TCDD contaminants leads to higher phosphorylation of VEcadherin in cardiac tissue suggesting that these cells have reduced connectivity. Small molecule inhibition of Src phosphorylation prevents contaminant stimulated phosphorylation of VEcadherin and rescues both cardiac function and gross morphology. Atlantic sturgeon hearts show parallels to contaminant exposed zebrafish cardiac phenotype at the tissue level. These data suggest that the mechanism for PCB and TCDD action in the heart is, in part, distinct from the canonical mechanism described in the literature and that cardiac defects are impacted by this nongenomic mechanism.
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http://dx.doi.org/10.1016/j.aquatox.2021.105794DOI Listing
April 2021

Toxic Effects of Polychlorinated Biphenyl Congeners and Aroclors on Embryonic Growth and Development.

Environ Toxicol Chem 2021 Jan 7;40(1):187-201. Epub 2020 Dec 7.

Department of Biology, Queens College, City University of New York, Queens, New York, USA.

Polychlorinated biphenyls (PCBs) cause significant health and reproductive problems in many vertebrates. Exposure during embryogenesis likely leads to defects in organ development, compromising survival and growth through adulthood. The present study identifies the impact of PCBs on the embryonic development of key organs and resulting consequences on survival and growth. Zebrafish embryos were treated with individual PCB congeners (126 or 104) or one of 4 Aroclor mixtures (1016, 1242, 1254, or 1260) and analyzed for changes in gross embryonic morphology. Specific organs were assessed for defects during embryonic development, using a variety of transgenic zebrafish to improve organ visualization. Resulting larvae were grown to adulthood while survival and growth were assayed. Embryonic gross development on PCB treatment was abnormal, with defects presenting in a concentration-dependent manner in the liver, pancreas, heart, and blood vessel organization. Polychlorinated biphenyl 126 treatment resulted in the most consistently severe and fatal phenotypes, whereas treatments with PCB 104 and Aroclors resulted in a range of more subtle organ defects. Survival of fish was highly variable although the growth rates of surviving fish were relatively normal, suggesting that maturing PCB-treated fish that survive develop compensatory strategies needed to reach adulthood. Life span analyses of fish from embryogenesis through adulthood, as in the present study, are scarce but important for the field because they help identify foci for further studies. Environ Toxicol Chem 2021;40:187-201. © 2020 SETAC.
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http://dx.doi.org/10.1002/etc.4908DOI Listing
January 2021

Growth and maturation in the zebrafish, Danio rerio: a staging tool for teaching and research.

Zebrafish 2014 Aug 30;11(4):396-406. Epub 2014 Jun 30.

1 Department of Biology, Queens College, City University of New York , Queens, New York.

Zebrafish have been increasingly used as a teaching tool to enhance the learning of many biological concepts from genetics, development, and behavior to the understanding of the local watershed. Traditionally, in both research and teaching, zebrafish work has focused on embryonic stages; however, later stages, from larval through adulthood, are increasingly being examined. Defining developmental stages based on age is a problematic way to assess maturity, because many environmental factors, such as temperature, population density, and water quality, impact growth and maturation. Fish length and characterization of key external morphological traits are considered better markers for maturation state. While a number of staging series exist for zebrafish, here we present a simplified normalization table of post-embryonic maturation well suited to both educational and research use. Specifically, we utilize fish size and four easily identified external morphological traits (pigment pattern, tail fin, anal fin, and dorsal fin morphology) to describe three larval stages, a juvenile stage, and an adult stage. These simplified maturation standards will be a useful tool for both educational and research protocols.
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http://dx.doi.org/10.1089/zeb.2014.0976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108942PMC
August 2014

Analysis of postembryonic heart development and maturation in the zebrafish, Danio rerio.

Dev Dyn 2012 Dec 5;241(12):1993-2004. Epub 2012 Nov 5.

Department of Biology, Queens College, City University of New York, Flushing New York and The Graduate Center, City University of New York, New York, New York, USA.

Background: Cardiac maturation is vital for animal survival and must occur throughout the animal's life. Zebrafish are increasingly used to model cardiac disease; however, little is known about how the cardiovascular system matures. We conducted a systematic analysis of cardiac maturation from larvae through to adulthood and assessed cardiac features influenced by genetic and environmental factors.

Results: We identified a novel step in cardiac maturation, termed cardiac rotation, where the larval heart rotates into its final orientation within the thoracic cavity with the atrium placed behind the ventricle. This rotation is followed by linear ventricle growth and an increase in the angle between bulbous arteriosus and the ventricle. The ventricle transitions from a rectangle, to a triangle and ultimately a sphere that is significantly enveloped by the atrium. In addition, trabeculae are similarly patterned in the zebrafish and humans, both with muscular fingerlike projections and muscle bands that span the cardiac chamber. Of interest, partial loss of atrial contraction in myosin heavy chain 6 (myh6/wea(hu423/+)) mutants result in the adult maintaining a larval cardiac form.

Conclusions: These findings serve as a foundation for the study of defects in cardiovascular development from both genetic and environmental factors.
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http://dx.doi.org/10.1002/dvdy.23882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446259PMC
December 2012

Heart dissection in larval, juvenile and adult zebrafish, Danio rerio.

J Vis Exp 2011 Sep 30(55). Epub 2011 Sep 30.

Department of Biology, Queens College, City University of New York, New York, USA.

Zebrafish have become a beneficial and practical model organism for the study of embryonic heart development, however, work examining post-embryonic through adult cardiac development has been limited. Examining the changing morphology of the maturing and aging heart are restricted by the lack of techniques available for staging and isolating juvenile and adult hearts. In order to analyze heart development over the fish's lifespan, we dissect zebrafish hearts at numerous stages and photograph them for further analysis. The morphological features of the heart can easily be quantified and individual hearts can be further analyzed by a host of standard methods. Zebrafish grow at variable rates and maturation correlates better with fish size than age, thus, post-fixation, we photograph and measure fish length as a gauge of fish maturation. This protocol explains two distinct, size dependent dissection techniques for zebrafish, ranging from larvae 3.5 mm standard length (SL) with hearts of 100 μm ventricle length (VL), to adults, with SL of 30 mm and VL 1mm or larger. Larval and adult fish have quite distinct body and organ morphology. Larvae are not only significantly smaller, they have less pigment and each organ is visually very difficult to identify. For this reason, we use distinct dissection techniques. We used pre-dissection fixation procedures, as we discovered that hearts dissected directly after euthanization have a more variable morphology, with very loose and balloon like atria compared with hearts removed following fixation. The fish fixed prior to dissection, retain in vivo morphology and chamber position (data not shown). In addition, for demonstration purposes, we take advantage of the heart (myocardial) specific GFP transgenic Tg(myl7:GFP)(twu34), which allows us to visualize the entire heart and is particularly useful at early stages in development when the cardiac morphology is less distinct from surrounding tissues. Dissection of the heart makes further analysis of the cell and molecular biology underlying heart development and maturation using in situ hybridization, immunohistochemistry, RNA extraction or other analytical methods easier in post-embryonic zebrafish. This protocol will provide a valuable technique for the study of cardiac development maturation and aging.
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http://dx.doi.org/10.3791/3165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230190PMC
September 2011