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Open Access Highly Accessed Research article

Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging

János Barna, Andrea Princz, Mónika Kosztelnik, Balázs Hargitai, Krisztina Takács-Vellai and Tibor Vellai*

Author Affiliations

Department of Genetics, Eötvös Loránd University, Pázmány Péter stny. 1/C, Budapest, H-1117, Hungary

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BMC Developmental Biology 2012, 12:32  doi:10.1186/1471-213X-12-32

Published: 1 November 2012

Abstract

Background

Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1) functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins) that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown.

Results

We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-β (transforming growth factor-beta) ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate) and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1) signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation.

Conclusion

Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1.

Keywords:
Heat shock factor-1; C. elegans; Dauer development; Aging; Signaling crosstalk