A Molecular Basis for Reciprocal Regulation between Pheromones and Hormones in Response to Dietary Cues in C. elegans.

Saeram Park,Jun Young Park,Young-Ki Paik

doi:10.3390/ijms21072366

Saeram Park, Jun Young Park + Show 1 more

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https://doi.org/10.3390/ijms21072366

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Abstract

Under stressful conditions, the early larvae of C. elegans enter dauer diapause, a non-aging period, driven by the seemingly opposite influence of ascaroside pheromones (ASCRs) and steroid hormone dafachronic acids (DAs). However, the molecular basis of how these small molecules engage in competitive crosstalk in coordination with insulin/IGF-1 signaling (IIS) remains elusive. Here we report a novel transcriptional regulatory pathway that seems to operate between the ASCR and DA biosynthesis under ad libitum (AL) feeding conditions or bacterial deprivation (BD). Although expression of the ASCR and DA biosynthetic genes reciprocally inhibit each other, ironically and interestingly, such dietary cue-mediated modulation requires the presence of the competitors. Under BD, induction of ASCR biosynthetic gene expression required DA, while ASCR suppresses the expression of the DA biosynthetic gene daf-36. The negative regulation of DA by ASCR was IIS-dependent, whereas daf-36 regulation appeared to be independent of IIS. These observations suggest that the presence of ASCR determines the IIS-dependency of DA gene expression regardless of dietary conditions. Thus, our work defines a molecular basis for a novel reciprocal gene regulation of pheromones and hormones to cope with stressful conditions during development and aging.

Highlights

Animals have adapted to survive by overcoming environmental stresses in various ways
Since dietary cues seem to be highly effective in determining the choice between alternative developmental programs, our aim was to clarify the differential regulation of ascaroside pheromones (ASCRs) and dafachronic acids (DAs) biosynthetic gene transcription by specific dietary cues
The feeding rate increased in proportion to the food amount; neither ASCR biosynthesis nor DA biosynthesis had any effects on the feeding rate, indicating that food intake is only influenced by food amount (Figure S1A)

Summary

Introduction

Animals have adapted to survive by overcoming environmental stresses in various ways. The nematode Caenorhabditis elegans secretes ascaroside pheromones (ASCRs); elevated pheromone levels are strong cues that induce dauer development under stressful conditions (e.g., starvation, overcrowding and high temperature) [1,2,3]. Since the first ASCR (daumone) was discovered [6], more than 160 ASCRs have been identified [7,8,9,10,11]. These ASCRs are biosynthesized in part through a peroxisomal fatty acid β-oxidation pathway where several genes (e.g., acox, maoc-1, dhs-28 and daf-22) are involved in the degradation of very long chain fatty acids into short chain fatty acids [8,10,12,13,14]. Due to its association with fatty acid metabolism, ASCR biosynthesis is usually activated by food abundance [15]

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