Social signals that regulate C. elegans development

项目总结

PROJECT SUMMARY Organismal development is a highly regulated process; its dysregulation can lead to disease. Yet, it is also flexible to make it responsive to the environment. One aspect of the environment is the social interactions among organisms. Whereas it is generally understood that these are important, the specific ways in which they affect organisms remain substantially unknown. Recent estimates, however, suggest that the impact of social interactions could be comparable in magnitude to the effect of genes. This necessitates the development of tractable model systems in which to study this problem. We addressed this challenge by studying the effects of social signals on development of a well-established model organism, C. elegans. We found that signals produced by males powerfully affect development and reproductive physiology of hermaphrodites, which are effectively female. Specifically, sensing the male presence alters hermaphrodite germline development, ensuring higher quality of gamete production until older age. Our experiments uncovered that these processes are controlled by highly conserved neuroendocrine signals that include insulins and serotonin. Taking advantage of the specific strengths of our model system and these preliminary findings we will investigate: (1) The specific developmental changes that take place in the germline and the gonad that supports it; (2) How neurons communicate the receipt of social signals to the gonad, where they affect the germline development; and (3) The role of behavior and sexual identity of neurons in responding to social signals appropriately. Importantly, although we study these problems in C. elegans, strikingly similar phenomena have been documented in all animals studied so far, including mammals. Moreover, defects neuroendocrine control of reproduction and sexual identity of cells have been implicated in numerous human disease conditions. This raises a possibility that social signals might play a role in their pathology. A better mechanistic understanding of these processes would lead to a better understanding of the underlying biology of these disease states. Because all molecular components we identified so far are highly conserved among all animals, we expect our work will offer insights for further research on the role of social signals in regulation of development and physiology. It may thus prove useful for a better understanding and, ultimately, treatment of relevant disease states in humans.