<i>spineless</i> provides a little backbone for dendritic morphogenesis: Figure 1.

Crews, Stephen T.; Brenman, Jay E.

doi:10.1101/gad.1487706

Cited by 21 publications

(18 citation statements)

References 37 publications

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“…It is unclear at this stage whether dioxin and the human AhR would activate in vivo cell migration under any physiological or pathological conditions. In this regard, it is interesting to note that the invertebrate Ahr, specifically in Caenorhabditis elegans and Drosophila, does not seem to mediate response to xenobiotics but is rather at least partially implicated in determining neuronal fate and migration, which is in line with our observations (Crews and Brenman, 2006;Qin et al, 2006;Wernet et al, 2006;McMillan and Bradfield, 2007). Studies of rodent AhR lead to a more balanced view of its functions (McMillan and Bradfield, 2007).…”

Section: Discussionsupporting

confidence: 86%

Nedd9/Hef1/Cas-L mediates the effects of environmental pollutants on cell migration and plasticity

et al. 2009

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Aryl hydrocarbon receptor (AhR), or dioxin receptor, is a transcription factor that induces adaptive metabolic pathways in response to environmental pollutants. Recently, other pathways were found to be altered by AhR and its ligands. Indeed, developmental defects elicited by AhR ligands suggest that additional cellular functions may be targeted by this receptor, including cell migration and plasticity. Here, we show that dioxin-mediated activation of Ahr induces Nedd9/Hef1/Cas-L, a member of the Cas protein family recently identified as a metastasis marker. The Hef1 gene induction is mediated by two xenobiotic responsive elements present in this gene promoter. Moreover, using RNA interference, we show that Nedd9/Hef1/Cas-L mediates the dioxin-elicited changes related to cell plasticity, including alterations of cellular adhesion and shape, cytoskeleton reorganization, and increased cell migration. Furthermore, we show that both E-cadherin repression and Jun N-terminal kinases activation by dioxin and AhR also depend on the expression of Nedd9/Hef1/Cas-L. Our study unveils, for the first time, a link between pollutants exposure and the induced expression of a metastasis marker and shows that cellular migration and plasticity markers are regulated by AhR and its toxic ligands.

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Section: Discussionsupporting

confidence: 86%

Nedd9/Hef1/Cas-L mediates the effects of environmental pollutants on cell migration and plasticity

et al. 2009

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“…The results in the present study support the finding that AHR plays an important role in mammalian CNS development. Indeed, even with no apparent ligand-binding properties, AHR analogs in Caenorhabditis elegans (Qin and Powell-Coffman 2004) and Drosophila (Crews and Brenman 2006) have been demonstrated to be associated with neuronal development.…”

Section: Discussionmentioning

confidence: 99%

In Utero and Lactational Exposure to PCBs in Mice: Adult Offspring Show Altered Learning and Memory Depending on Cyp1a2 and Ahr Genotypes

Curran

Nebert²,

Genter³

et al. 2011

Environ Health Perspect

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Background: Both coplanar and noncoplanar polychlorinated biphenyls (PCBs) exhibit neurotoxic effects in animal studies, but individual congeners do not always produce the same effects as PCB mixtures. Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; because CYP1A2 is known to sequester coplanar PCBs and because AHR ligands include coplanar PCBs, both genotypes can affect PCB response.Objectives: We aimed to develop a mouse paradigm with extremes in Cyp1a2 and Ahr genotypes to explore genetic susceptibility to PCB-induced developmental neurotoxicity using an environmentally relevant mixture of PCBs.Methods: We developed a mixture of eight PCBs to simulate human exposures based on their reported concentrations in human tissue, breast milk, and food supply. We previously characterized specific differences in PCB congener pharmacokinetics and toxicity, comparing high-affinity–AHR Cyp1a2 wild-type [Ahrb1_Cyp1a2(+/+)], poor-affinity–AHR Cyp1a2 wild-type [Ahrd_Cyp1a2(+/+)], and high-affinity–AHR Cyp1a2 knockout [Ahrb1_Cyp1a2(–/–)] mouse lines [Curran CP, Vorhees CV, Williams MT, Genter MB, Miller ML, Nebert DW. 2011. In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes. Toxicol Sci 119:189–208]. Dams received a mixture of three coplanar and five noncoplanar PCBs on gestational day 10.5 and postnatal day (PND) 5. In the present study we conducted behavioral phenotyping of exposed offspring at PND60, examining multiple measures of learning, memory, and other behaviors.Results: We observed the most significant deficits in response to PCB treatment in Ahrb1_Cyp1a2(–/–) mice, including impaired novel object recognition and increased failure rate in the Morris water maze. However, all PCB-treated genotypes showed significant differences on at least one measure of learning or behavior.Conclusions: High levels of maternal hepatic CYP1A2 offer the most important protection against deficits in learning and memory in offspring exposed to a mixture of coplanar and noncoplanar PCBs. High-affinity AHR is the next most important factor in protection of offspring.

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“…Yet another developmental role of the D. melanogaster AHR homolog is in controlling dendrite morphology on dendritic arborization (da) sensory neurons in the fly peripheral nervous system [48,49]. The effect of ss varies in different types of da neurons, with the end result of diversifying dendrite morphology.…”

Section: Ahrs In Protostomes: Key Roles In Development Of Sensory mentioning

confidence: 99%

“…The common theme of the research in C. elegans and D. melanogaster , with circumstantial support from studies in the cnidarian N. vectensis , is one of pleiotropic roles of AHR in controlling the development (cell fate and differentiation) and function of sensory structures and neural systems [18,32,33,49]. These functions appear to involve both activation and repression of gene expression by AHR [37,43].…”

Section: Ahrs In Protostomes: Key Roles In Development Of Sensory mentioning

confidence: 99%

“…Studies in protostomes provide evidence for pleiotropic roles of AHR in controlling the development and function of sensory structures and neural systems and these have been suggested as ancestral roles of AHR [18,32,33,37,49]. Possible roles of AHR in sensory/neural systems are less well understood in vertebrate animals, but results from AHR loss-of-function studies and effects of TCDD on neural development in fish and mammals [96–103] suggest that this is an area worth further exploration.…”

Section: Functional Divergence Of a Pleiotropic Protein: Shared Anmentioning

confidence: 99%

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Diversity as opportunity: Insights from 600 million years of AHR evolution

Hahn

Karchner

Merson

2017

Current Opinion in Toxicology

107

111

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The aryl hydrocarbon receptor (AHR) was for many years of interest only to pharmacologists and toxicologists. However, this protein has fundamental roles in biology that are being revealed through studies in diverse animal species. The AHR is an ancient protein. AHR homologs exist in most major groups of modern bilaterian animals, including deuterostomes (chordates, hemichordates, echinoderms) and the two major clades of protostome invertebrates [ecdysozoans (e.g. arthropods and nematodes) and lophotrochozoans (e.g. molluscs and annelids)]. AHR homologs also have been identified in cnidarians such as the sea anemone Nematostella and in the genome of Trichoplax, a placozoan. Bilaterians, cnidarians, and placozoans form the clade Eumetazoa, whose last common ancestor lived approximately 600 million years ago (MYA). The presence of AHR homologs in modern representatives of all these groups indicates that the original eumetazoan animal possessed an AHR homolog. Studies in invertebrates and vertebrates reveal parallel functions of AHR in the development and function of sensory neural systems, suggesting that these may be ancestral roles. Vertebrate animals are characterized by the expansion and diversification of AHRs, via gene and genome duplications, from the ancestral protoAHR into at least five classes of AHR-like proteins: AHR, AHR1, AHR2, AHR3, and AHRR. The evolution of multiple AHRs in vertebrates coincided with the acquisition of high-affinity binding of halogenated and polynuclear aromatic hydrocarbons and the emergence of adaptive functions involving regulation of xenobiotic-metabolizing enzymes and roles in adaptive immunity. The existence of multiple AHRs may have facilitated subfunction partitioning and specialization of specific AHR types in some taxa. Additional research in diverse model and non-model species will continue to enrich our understanding of AHR and its pleiotropic roles in biology and toxicology.

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spineless provides a little backbone for dendritic morphogenesis: Figure 1.

Cited by 21 publications

References 37 publications

Nedd9/Hef1/Cas-L mediates the effects of environmental pollutants on cell migration and plasticity

Nedd9/Hef1/Cas-L mediates the effects of environmental pollutants on cell migration and plasticity

In Utero and Lactational Exposure to PCBs in Mice: Adult Offspring Show Altered Learning and Memory Depending on Cyp1a2 and Ahr Genotypes

Diversity as opportunity: Insights from 600 million years of AHR evolution

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