DBL-1, a TGF-β, is essential for Caenorhabditis elegans aversive olfactory learning

Abstract

The TGF-β superfamily is conserved throughout metazoan, and its members play essential roles in development and disease. TGF-β has also been implicated in adult neural plasticity. However, the underlying mechanisms are not well understood. Here we report that DBL-1, a Caenorhabditis elegans TGF-β homolog known to control body morphology and immunity, is essential for aversive olfactory learning of potentially harmful bacteria food. We show that DBL-1 generated by the AVA command interneurons, which are critical for sensorimotor responses, regulates aversive olfactory learning, and that the activity of the type I TGF-β receptor SMA-6 in the hypodermis is needed during adulthood to generate olfactory plasticity. These spatial and temporal mechanisms are critical for the DBL-1 signaling to achieve its diverse functions in development and adult neural plasticity. Interestingly, aversive training decreases AVA calcium response, leading to an increase in the DBL-1 signal secreted from AVA, revealing an experience-dependent change that can underlie the role of TGF-β signaling in mediating plasticity.experience-dependent secretion | molecular and cellular mechanisms for TGF-beta pathway in learning

The olfactory neuron AWC promotes avoidance to normally palatable food following chronic dietary restriction

“…4E,F). Expressing the SMA-6 receptor, using previously reported strains able to rescue sma-6 aversive olfactory learning defects (Zhang and Zhang, 2012), in hypodermis (using the col-12

Fig. 4. HEN-1 and the DBL-1/Sma pathway regulate food-avoidance behavior.

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Behavioral avoidance of pathogenic bacteria by Caenorhabditis elegans

“…INS-6 secreted from ASI antagonizes expression of another insulin-like peptide, INS-7, in a second set of neurons, and the authors hypothesize that secreted INS-7, in turn, negatively affects aversive learning by antagonizing the insulin receptor DAF-2 [25]. In a second study, the secreted TGF-b ligand DBL-1 was also shown to be necessary for the aversive learning response on P. aeruginosa [26]. Thus, at least three neuropeptides promote aversive learning on P. aeruginosa, two of which -INS-6 and INS-7 -act through the aforementioned ADF modulatory circuit.…”

Chemosensation of Bacterial Secondary Metabolites Modulates Neuroendocrine Signaling and Behavior of C. elegans

“…DAF-7 functions in the neuroendocrine regulation of diverse aspects of organismal development and physiology, including the dauer developmental decision, foraging and aggregation behaviors, quiescence, metabolism, and longevity (de Bono et al, 2002; Gallagher et al, 2013; Greer et al, 2008; Milward et al, 2011; Shaw et al, 2007; Swanson and Riddle, 1981). In addition, another C. elegans TGF-β-family ligand, DBL-1, has been shown to regulate olfactory aversive learning and antifungal defenses (Zhang and Zhang, 2012; Zugasti and Ewbank, 2009). Expression of daf-7 is limited to the ASI pair of chemosensory neurons and has been shown to respond to the availability of bacterial food (Ren et al, 1996; Schackwitz et al, 1996).…”