A common muscarinic pathway for diapause recovery in the distantly related nematode species Caenorhabditis elegans and Ancylostoma caninum

Abstract

Converging TGF-␤ and insulin-like neuroendocrine signaling pathways regulate whether Caenorhabditis elegans develops reproductively or arrests at the dauer larval stage. We examined whether neurotransmitters act in the dauer entry or recovery pathways. Muscarinic agonists promote recovery from dauer arrest induced by pheromone as well as by mutations in the TGF-␤ pathway. Dauer recovery in these animals is inhibited by the muscarinic antagonist atropine. Muscarinic agonists do not induce dauer recovery of either daf-2 or age-1 mutant animals, which have defects in the insulin-like signaling pathway. These data suggest that a metabotropic acetylcholine signaling pathway activates an insulin-like signal during C. elegans dauer recovery. Analogous and perhaps homologous cholinergic regulation of mammalian insulin release by the autonomic nervous system has been noted. In the parasitic nematode Ancylostoma caninum, the dauer larval stage is the infective stage, and recovery to the reproductive stage normally is induced by host factors. Muscarinic agonists also induce and atropine potently inhibits in vitro recovery of A. caninum dauer arrest. We suggest that host or parasite insulin-like signals may regulate recovery of A. caninum and could be potential targets for antihelminthic drugs.

O-Linked-N-Acetylglucosamine Cycling and Insulin Signaling Are Required for the Glucose Stress Response inCaenorhabditis elegans

“…Although mutations in both the insulin signaling and the TGF-b pathways can lead to dauer entry, these pathways are known to have overlapping but distinct regulatory roles. For example, recovery from dauer seems to require insulin signaling but not TGF-b signaling (Tissenbaum et al 2000). In humans, both insulin signaling and the TGF-b signaling pathways respond to glucose and are implicated in diseases of glucose toxicity, like diabetes (reviewed in Zhu et al 2007).…”

Blood-feeding in the young adult filarial wormsLitomosoides sigmodontis

“…TGF-b and its homologues have been implicated in development of Caenorhabditis elegans (cf. Tissenbaum et al 2000), that of Ancylostoma caninum (cf. Arasu, 2001), and found in Brugia filariae (Gomez-Escobar, Gregory & Maizels, 1998 ;Gomez-Escobar, Lewis & Maizels, 2000).…”

Specific insulin-like peptides encode sensory information to regulate distinct developmental processes

“…Many of the ILPs are expressed in overlapping subsets of sensory neurons and/or interneurons, including the sensory neurons (Kodama et al, 2006;Li et al, 2003;Pierce et al, 2001) that regulate dauer entry or exit (Bargmann and Horvitz, 1991;Kim et al, 2009;Ouellet et al, 2008;Schackwitz et al, 1996). Interestingly, the mechanism that regulates entry into dauer arrest differs from the mechanism that regulates exit from this state, not only at the neuronal but also at the molecular level (Bargmann and Horvitz, 1991;Kim et al, 2009;Ouellet et al, 2008;Schackwitz et al, 1996;Tissenbaum et al, 2000). Since the endogenous roles of individual ILPs in these developmental switches are unknown, the different ILP gene expression patterns have led us to consider the hypothesis that they encode discrete sets of sensory information to regulate dauer entry versus exit.…”