Uncovering the role of Insulin/FoxO signaling in stem cells in Hydra to understand how stem cell dynamics is responding to external signals and metabolic state in an early emerging metazoan

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One of the major challenges in developmental biology is to understand how cells become specified and organised in complex tissues. How a cell chooses to proliferate or to differentiate is an important issue in stem cell biology and as critical to human stem cells as it is to any other stem cell. Here I propose an integrated approach to explore molecular mechanisms underlying interstitial stem cell regulation in Hydra, a member of one of the earliest diverging animal phyla, the Cnidaria. Previous studies have identified a number of essential factors affecting interstitial stem cell proliferation and differentiation. With advances in transgenic technology, it has become possible not only to genetically label specific cell lineages in Hydra but also to genetically manipulate all three stem cell lineages. Little is known, however, about the molecular mechanisms controlling stem cell behavior. Our work attempts to bridge this gap, by combining genetic, cell biological, molecular and computational approaches to identify the genes which are directly involved in control of stem cell behavior and to understand how these genes work together in the context of the native microenvironment. The focus will be on three different aspects of interstitial stem cell biology in Hydra: (i) discovering specific molecular markers for these cells, (ii) identifying key regulator proteins affecting stem cell behavior, and (iii) defining the cellular and molecular microenvironement surrounding these cells. The study will not only indicate the role for interstitial stem cell specific genes but also reveal the complexity of cell fate regulation in stem cells at the basis of animal evolution.