The Caenorhabditis elegans aryl hydrocarbon receptor, AHR-1, regulates neuronal development

Abstract

The mammalian aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxic effects of dioxins and related compounds. Dioxins have been shown to cause a range of neurological defects, but the role of AHR during normal neuronal development is not known. Here we investigate the developmental functions of ahr-1, the Caenorhabditis elegans aryl hydrocarbon receptor homolog. We show that ahr-1:GFP is expressed in a subset of neurons, and we demonstrate that animals lacking ahr-1 function have specific defects in neuronal differentiation, as evidenced by changes in gene expression, aberrant cell migration, axon branching, or supernumerary neuronal processes. In ahr-1-deficient animals, the touch receptor neuron AVM and its sister cell, the interneuron SDQR, exhibit cell and axonal migration defects. We show that dorsal migration of SDQR is mediated by UNC-6/Netrin, SAX-3/Robo, and UNC-129/TGFbeta, and this process requires the functions of both ahr-1 and its transcription factor dimerization partner aha-1. We also document a role for ahr-1 during the differentiation of the neurons that contact the pseudocoelomic fluid. In ahr-1-deficient animals, these neurons are born but they do not express the cell-type-specific markers gcy-32:GFP and npr-1:GFP at appropriate levels. Additionally, we show that ahr-1 expression is regulated by the UNC-86 transcription factor. We propose that the AHR-1 transcriptional complex acts in combination with other intrinsic and extracellular factors to direct the differentiation of distinct neuronal subtypes. These data, when considered with the neurotoxic effects of AHR-activating pollutants, support the hypothesis that AHR has an evolutionarily conserved role in neuronal development.

Transmembrane protein MIG-13 links the Wnt signaling and Hox genes to the cell polarity in neuronal migration

“…S1F and Fig. S2E), Pgcy-32 expresses in Q.ap, Pegl-46 expresses in Q.a/Q.ap and Q.pa/Q.paa, and Pmec-7 expresses in Q.paa (24)(25)(26) (Fig. 2A).…”

Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism

“…Supporting the view that AhR is not a mere xenobiotic sensor controlling a metabolic cascade, invertebrate species do possess AhR orthologs with no known endogenous or exogenous ligand. In Caenorhabditis elegans development, the corresponding gene has recently been shown to play a role in proper migration and differentiation of specific neurons (Huang et al, 2004;Qin and Powell-Coffman, 2004). In addition, AhR null mice exhibit a number of developmental defects (Fernandez-Salguero et al, 1995).…”

Circadian rhythms identified in Caenorhabditis elegans by in vivo long-term monitoring of a bioluminescent reporter

“…Several proteins have been described as putative homologs to the insect/mammalian core clock genes, notably the aryl hydrocarbon receptor associated protein (AHA-1), the abnormal cell lineage 42 protein isoforms b/c (LIN-42b/c), or timeless related protein (TIM-1), which show different degrees of homology to CLOCK, PERIOD, and TIMELESS, respectively (20,49). However, these genes thus far have been reported to play developmental roles in the nematode (21)(22)(23), and none has been demonstrated to show circadian rhythmicity at the mRNA level (14,19). To construct a classical TTFL (5) with a negative feedback loop, at least one of these genes should cycle.…”

“…Recent exhaustive bioinformatics searches have identified proteins of relatively high homology to clock components from other species (20). However, these homolog genes play a key role in the developmental program of C. elegans (21)(22)(23), and their function in the circadian clock of the nematode is not clear.…”