Biology subjects

Hahn, M. E.

Publications and source records attributed to Hahn, M. E..

6 recordsLinked to original sources

bioRxiv2024

Environmental and Population influences on Mummichog (Fundulus heteroclitus) Gut Microbiomes

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, or gut microbiome, particularly when activated by the model toxic pollutant 3,3,4,4,5-pentachlorobiphenyl (PCB-126) and other dioxin-like compounds. In order 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) and the other from a non-polluted location (Scorton Creek, MA), as well as laboratory-reared F2 generation fish originating from each of these populations. We examined the bacteria and archaea associated with the gut of these fish using amplicon sequencing of small subunit ribosomal RNA genes. Fish living in the PCB-polluted site had high microbial alpha and beta diversity and an altered microbial network structure compared to fish from the non-polluted 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 the 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 has 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.

ecology↗

bioRxiv2023

Independently evolved pollution resistance in four killifish populations is largely explained by few variants of large effect

The genetic architecture of phenotypic traits can affect the mode and tempo of trait evolution. Human-altered environments can impose strong natural selection, where successful evolutionary adaptation requires swift and large phenotypic shifts. In these scenarios, theory predicts the influence of few adaptive variants of large effect, but empirical studies that have revealed the genetic architecture of rapidly evolved phenotypes are rare, especially for populations inhabiting polluted environments. Fundulus killifish have repeatedly evolved adaptive resistance to extreme pollution in urban estuaries. Prior studies, including genome scans for signatures of natural selection, have revealed some of the genes and pathways important for evolved pollution resistance, and provide context for the genotype-phenotype association studies reported here. We created multiple quantitative trait locus (QTL) mapping families using progenitors from four different resistant populations, and genetically mapped variation in sensitivity (developmental perturbations) following embryonic exposure to a model toxicant PCB-126. We found that a few large-effect QTL loci accounted for resistance to PCB- mediated developmental toxicity. QTLs harbored candidate genes that govern the regulation of aryl hydrocarbon receptor (AHR) signaling, where some (but not all) of these QTL loci were shared across all populations, and some (but not all) of these loci showed signatures of recent natural selection in the corresponding wild population. Some strong candidate genes for PCB resistance inferred from genome scans in wild populations were identified as QTL, but some key candidate genes were not. We conclude that rapidly evolved resistance to the developmental defects normally caused by PCB-126 is governed by few genes of large effect. However, other aspects of resistance beyond developmental phenotypes may be governed by additional loci, such that comprehensive resistance to PCB-126, and to the mixtures of chemicals that distinguish urban estuaries more broadly, may be more genetically complex.

evolutionary biology↗

bioRxiv2022

Developmental exposure to domoic acid targets reticulospinal neurons and leads to aberrant myelination in the spinal cord

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, which 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.

pharmacology and toxicology↗

bioRxiv2021

Developmental exposure to domoic acid disrupts startle response behavior and circuitry

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 are largely unknown. To assess these, we exposed zebrafish embryos to DomA during the previously identified window of susceptibility (2 days post-fertilization) 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 the probability of eliciting a startle after auditory/vibrational or electrical stimuli and led to the dramatic reduction of one type of startle, short latency c-start (SLC) responses. Furthermore, DomA-exposed larvae had altered kinematics of both SLC and long latency c-start (LLC) startle responses, 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 SLC responses 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 leads to startle deficits by targeting specific subsets of neurons. These findings provide mechanistic insights into the neurodevelopmental effects of excess glutamatergic signaling caused by exposure to DomA. It further provides a model for using the startle response circuit to identify neuronal populations targeted by toxin or toxicant exposures. Summary statementWe used the zebrafish startle response as a tool to identify sensory-motor deficits and the loss of specific neural populations after developmental exposure to the harmful algal bloom toxin domoic acid. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/425996v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1aac99aorg.highwire.dtl.DTLVardef@199cb73org.highwire.dtl.DTLVardef@1fc1a00org.highwire.dtl.DTLVardef@f1dff_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2019

Domoic acid disruption of neurodevelopment and behaviorinvolves altered myelination in the spinal cord

Harmful algal blooms (HABs) produce potent neurotoxins that threaten human health. Early life exposure to low levels of the HAB toxin domoic acid (DomA) produces long-lasting behavioral deficits, but the mechanisms involved are unknown. Using zebrafish, we investigated the developmental window of susceptibility to low doses of DomA and examined cellular and molecular targets. Larvae exposed to DomA at 2 days post-fertilization (dpf), but not at 1 or 4 dpf, showed consistent deficits in startle behavior including reduced responsiveness and altered kinematics. Similarly, myelination in the spinal cord was disorganized after exposure only at 2 dpf. Time-lapse imaging revealed disruption of the initial stages of myelination. DomA down-regulated genes required for maintaining myelin structure and the axonal cytoskeleton. These results identify a developmental window of susceptibility to DomA-induced behavioral deficits involving altered gene expression and disrupted myelin structure, and establish a zebrafish model for investigating the underlying mechanisms. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=34 SRC="FIGDIR/small/842294v1_ufig1.gif" ALT="Figure 1"> View larger version (8K): org.highwire.dtl.DTLVardef@198491org.highwire.dtl.DTLVardef@14e6e84org.highwire.dtl.DTLVardef@39d118org.highwire.dtl.DTLVardef@1cea6c7_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2019

An Aryl Hydrocarbon Receptor from the Caecilian Gymnopis multiplicata Suggests Low Dioxin Affinity in the Ancestor of All Three Amphibian Orders

The aryl hydrocarbon receptor (AHR) plays pleiotropic roles in the development and physiology of vertebrates in conjunction with xenobiotic and endogenous ligands. It is best known for mediating the toxic effects of dioxin-like pollutants such as 2,3,7,8-tetracholordibenzo-p-dioxin (TCDD). While most vertebrates possess at least one AHR that binds TCDD tightly, amphibian AHRs bind TCDD with very low affinity. Previous analyses of AHRs from Xenopus laevis (a frog; order Anura) and Ambystoma mexicanum (a salamander; order Urodela) identified three amino acid residues in the ligand-binding domain (LBD) that underlie low-affinity binding. In X. laevis AHR1{beta}, these are A354, A370, and N325. Here we extend the analysis of amphibian AHRs to the caecilian Gymnopis multiplicata, representing the remaining extant amphibian order, Apoda. G. multiplicata AHR groups with the monophyletic vertebrate AHR/AHR1 clade. The LBD includes all three signature residues of low TCDD affinity, and a structural homology model suggests that its architecture closely resembles those of other amphibians. In transactivation assays, the EC50 for reporter gene induction by TCDD was 17.17 nM, comparable to X. laevis AhR1{beta} (26.23 nM) and Ambystoma AHR (34.09 nM) and dramatically higher than mouse AhR (0.13 nM), a trend generally reflected in direct measures of TCDD binding. These shared properties distinguish amphibian AHRs from the high-affinity proteins typical of both more ancient vertebrate groups (teleost fish) and those that appeared more recently (tetrapods). We suggest that AHRs with low TCDD affinity represent a basal characteristic that evolved in a common ancestor of all three extant amphibian groups.\n\nResearch HighlightsO_LIA caecilian aryl hydrocarbon receptor exhibits low dioxin binding and sensitivity.\nC_LIO_LIThe proteins ligand-binding domain resembles frog and salamander AHRs in structure and function.\nC_LIO_LIAHR with low dioxin affinity likely evolved in a common ancestor of all three extant amphibian groups.\nC_LI\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=190 HEIGHT=200 SRC=\"FIGDIR/small/750653v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (61K):\norg.highwire.dtl.DTLVardef@1a8b05eorg.highwire.dtl.DTLVardef@1d308e4org.highwire.dtl.DTLVardef@1eceb1dorg.highwire.dtl.DTLVardef@13fe8fd_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗