TGF-β signaling can act from multiple tissues to regulate C. elegans body size

Background: Regulation of organ and body size is a fundamental biological phenomenon, requiring tight coordination between multiple tissues to ensure accurate proportional growth. In C. elegans, a TGF-beta pathway is the major regulator of body size and also plays a role in the development of the male tail, and is thus referred to as the TGF-beta/Sma/Mab (for small and male abnormal) pathway. Mutations in components of this pathway result in decreased growth of animals during larval stages, with Sma mutant adults of the core pathway as small as similar to 60-70% the length of normal animals. The currently accepted model suggests that TGF-beta/Sma/Mab pathway signaling in the C. elegans hypodermis is both necessary and sufficient to control body length. However, components of this signaling pathway are expressed in other organs, such as the intestine and pharynx, raising the question of what the function of the pathway is in these organs. Results: Here we show that TGF-beta/Sma/Mab signaling is required for the normal growth of the pharynx. We further extend the current model and show that the TGF-beta/Sma/Mab pathway can function in multiple tissues to regulate body and organ length. Specifically, we find that pharyngeal expression of the SMAD protein SMA-3 partially rescues both pharynx length and body length of sma-3 mutants. Conclusions: Overall, our results support a model in which the TGF-beta/Sma/Mab signaling pathway can act in multiple tissues, activating one or more downstream secreted signals that act non cell-autonomously to regulate overall body length in C. elegans.