TGFβ-like DAF-7 acts as a systemic signal for autophagy regulation in C. elegans

In response to stress conditions, autophagy activity in multicellular organisms is systemically modulated to ensure maintenance of cellular homeostasis at an organismal level. Very little is known about the intercellular signals that elicit the long-range organism-wide autophagy response. Here we showed that during Caenorhabditis elegans development, loss of cuticle annular furrow collagens elicits autophagy in the hypodermis, intestine, and muscle. The cilia of sensory neurons with cuticle-localized endings are essential for triggering this systemic response. The TGFβ-like molecule DAF-7, which is secreted in part from a specific pair of ciliated neurons, acts as a systemic factor that activates a canonical TGFβ signaling pathway in distant tissues to induce autophagy. We also showed that AAK-2/AMPK and the STAT-like protein STA-2 act differentially in different tissues for autophagy activation. Our study reveals a circuit that senses and transduces the signal from the damaged cuticle to activate systemic autophagy during animal development.