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ABSTRACT The mummichog,Fundulus heteroclitus, an abundant estuarine fish broadly distributed along the eastern coast of North America, has repeatedly evolved tolerance to otherwise lethal levels of aromatic hydrocarbon exposure. This tolerance is linked to reduced activation of the aryl hydrocarbon receptor (AHR) signaling pathway. In other animals, the AHR has been shown to influence the gastrointestinal-associated microbial community, particularly when activated by the model toxic pollutant 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126) and other dioxin-like compounds. To understand host population and PCB-126 exposure effects on mummichog gut microbiota, we sampled two populations of wild fish, one from a PCB-contaminated environment (New Bedford Harbor, MA, USA) and the other from a much less polluted location (Scorton Creek, MA, USA), as well as laboratory-reared F2 generation fish originating from each of these populations. We examined the microbes associated with the gut of these fish using amplicon sequencing of bacterial and archaeal small subunit ribosomal RNA genes. Fish living in the PCB-polluted site had high microbial alpha and beta diversity compared to fish from the low PCB site. These differences between wild fish were not present in laboratory-reared F2 fish that originated from the same populations. Microbial compositional differences existed between wild and lab-reared fish, with the wild fish dominated by Vibrionaceae and the lab-reared fish by Enterococceae. These results suggest that mummichog habitat and/or environmental conditions have a stronger influence on the mummichog gut microbiome compared to population or hereditary-based influences. Mummichog are important eco-evolutionary model organisms; this work reveals their importance for exploring host-environmental-microbiome dynamics. IMPORTANCEThe mummichog fish, a common resident of North America's east coast estuaries, has evolved the ability to survive in waters contaminated with toxic chemicals that would typically be deadly. Our study investigates how living in and adapting to these toxic environments may affect their gut microbiomes. We compared mummichogs from a polluted area in Massachusetts with those from a non-polluted site and found significant differences in their gut microbes. Interestingly, when we raised the next generation of these fish in a lab, these differences disappeared, suggesting that the environment plays a more crucial role in shaping the gut microbiome than genetics. Understanding these changes helps shed light on how animals and their associated microbiomes adapt to pollution, which can inform conservation efforts and our broader understanding of environmental impacts on host-microbe dynamics. 

Saxitoxin (STX) is a potent neurotoxin naturally produced by dinoflagellates and cyanobacteria. STX inhibits voltage-gated sodium channels (VGSCs), affecting the propagation of action potentials. Consumption of seafood contaminated with STX is responsible for paralytic shellfish poisoning (PSP). Humans are among the species most sensitive to PSP; neurological symptoms of exposure range from tingling of the extremities to severe paralysis. The objective of this study was to determine the effects of STX exposure on developmental processes during early embryogenesis. This study was designed to test the hypothesis that early developmental exposure to STX would disrupt key processes, particularly those related to neural development. Zebrafish embryos were exposed to STX (24 or 48 pg) or vehicle (0.3 mM HCl) at 6 hours post fertilization (hpf) via microinjection. There was no overt toxicity but starting at 36 hpf there was a temporary lack of pigmentation in STX-injected embryos, which resolved by 72 hpf. Using high performance liquid chromatography, we found that STX was retained in embryos up to 72 hpf in a dose-dependent manner. Temporal transcriptional profiling of embryos exposed to 48 pg STX per embryo revealed no differentially expressed genes (DEGs) at 24 hpf, but at 36 and 48 hpf, there were 3547 and 3356 DEGs, respectively. KEGG pathway
analysis revealed significant enrichment of genes related to focal adhesion, adherens junction and regulation of
actin cytoskeleton, suggesting that cell-cell and cell-extracellular matrix interactions were affected by STX. Genes affected are critical for axonal growth and the
development of functional neural
networks. We confirmed these findings by visualizing axonal defects in transgenic zebrafish with fluorescently labeled sensory neurons. In addition, our gene expression results suggest that STX exposure affects both canonical and noncanonical functions of VGSCs. Given the fundamental role of VGSCs in both physiology and development, these findings offer valuable insights into effects of exposure to neurotoxins. 

A diversity of chemicals are intentionally added to plastics to enhance their properties and aid in manufacture. Yet, the accumulated chemical composition of these materials is essentially unknown even to those within the supply chain, let alone to consumers or recyclers. Recent legislated and voluntary commitments to increase recycled content in plastic products highlight the practical challenges wrought by these chemical mixtures, amid growing public concern about the impacts of plastic-associated chemicals on environmental and human health. In this Perspective, we offer guidance for plastics manufacturers to collaborate across sectors and critically assess their use of added chemicals. The ultimate goal is to use fewer and better additives to promote a circular plastics economy with minimal risk to humans and the environment. 

Abstract Harmful algal blooms (HABs) produce neurotoxins that affect human health. Developmental exposure of zebrafish embryos to the HAB toxin domoic acid (DomA) causes myelin defects, loss of reticulospinal neurons, and behavioral deficits. However, it is unclear whether DomA primarily targets myelin sheaths, leading to the loss of reticulospinal neurons, or reticulospinal neurons, causing myelin defects. Here, we show that while exposure to DomA at 2 dpf did not reduce the number of oligodendrocyte precursors prior to myelination, it led to fewer myelinating oligodendrocytes that produced shorter myelin sheaths and aberrantly wrapped neuron cell bodies. DomA-exposed larvae lacked Mauthner neurons prior to the onset of myelination, suggesting that axonal loss is not secondary to myelin defects. The loss of the axonal targets may have led oligodendrocytes to inappropriately myelinate neuronal cell bodies. Consistent with this, GANT61, a GLI1/2 inhibitor that reduces oligodendrocyte number, caused a reduction in aberrantly myelinated neuron cell bodies in DomA-exposed fish. Together, these results suggest that DomA initially alters reticulospinal neurons and the loss of axons causes aberrant myelination of nearby cell bodies. The identification of initial targets and perturbed cellular processes provides a mechanistic understanding of how DomA alters neurodevelopment, leading to structural and behavioral phenotypes. 

Abstract Harmful algal blooms produce potent neurotoxins that accumulate in seafood and are hazardous to human health. Developmental exposure to the harmful algal bloom toxin, domoic acid (DomA), has behavioral consequences well into adulthood, but the cellular and molecular mechanisms of DomA developmental neurotoxicity are largely unknown. To assess these, we exposed zebrafish embryos to DomA during the previously identified window of susceptibility and used the well-known startle response circuit as a tool to identify specific neuronal components that are targeted by exposure to DomA. Exposure to DomA reduced startle responsiveness to both auditory/vibrational and electrical stimuli, and even at the highest stimulus intensities tested, led to a dramatic reduction of one type of startle (short latency c-starts). Furthermore, DomA-exposed larvae had altered kinematics for both types of startle responses tested, exhibiting shallower bend angles and slower maximal angular velocities. Using vital dye staining, immunolabelling, and live imaging of transgenic lines, we determined that while the sensory inputs were intact, the reticulospinal neurons required for short latency c-starts were absent in most DomA-exposed larvae. Furthermore, axon tracing revealed that DomA-treated larvae also showed significantly reduced primary motor neuron axon collaterals. Overall, these results show that developmental exposure to DomA targets large reticulospinal neurons and motor neuron axon collaterals, resulting in measurable deficits in startle behavior. They further provide a framework for using the startle response circuit to identify specific neural populations disrupted by toxins or toxicants and to link these disruptions to functional consequences for neural circuit function and behavior. 

Abstract Over the last 2 decades, the zebrafish (Danio rerio) has emerged as a stellar model for unraveling molecular signaling events mediated by the aryl hydrocarbon receptor (AHR), an important ligand-activated receptor found in all eumetazoan animals. Zebrafish have 3 AHRs—AHR1a, AHR1b, and AHR2, and studies have demonstrated the diversity of both the endogenous and toxicological functions of the zebrafish AHRs. In this contemporary review, we first highlight the evolution of the zebrafish ahr genes, and the characteristics of the receptors including developmental and adult expression, their endogenous and inducible roles, and the predicted ligands from homology modeling studies. We then review the toxicity of a broad spectrum of AHR ligands across multiple life stages (early stage, and adult), discuss their transcriptomic and epigenetic mechanisms of action, and report on any known interactions between the AHRs and other signaling pathways. Through this article, we summarize the promising research that furthers our understanding of the complex AHR pathway through the extensive use of zebrafish as a model, coupled with a large array of molecular techniques. As much of the research has focused on the functions of AHR2 during development and the mechanism of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) toxicity, we illustrate the need to address the considerable knowledge gap in our understanding of both the mechanistic roles of AHR1a and AHR1b, and the diverse modes of toxicity of the various AHR ligands.