Molecular mechanisms of lipid signaling in the developing nervous system

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During the development of the central nervous system, neuronal activity drives the specification and maturation of synaptic connections. The process of neuronal maturation and formation of functional contacts is tightly controlled by expression of numerous genes regulated by activation of various signaling pathways across development. Fatty acids (lipids) are major components of neuronal cell membranes and serve as a supply of signaling molecules, such as prostaglandin E2 (PGE2). It has been shown that in the nervous system PGE2 can mediate responses such as neuronal plasticity, learning and memory, increase of dendritic spines and pain response. This study will investigate the molecular mechanisms associated with PGE2 signaling in the nervous system. The goals of the proposed research program are (1) to understand the role of PGE2 signaling and its downstream effectors in early neuronal development, (2) how abnormal signaling of this pathway can adversely interfere with cell function and result in potential developmental defects of the nervous system, and (3) to provide evidence for cross talk between PGE2 signaling pathway and another key pathways essential for early patterning of the nervous system. This study will further our knowledge of how the brain uses cooperative signaling of various pathways for its development and how changes in signaling of these pathways may contribute to abnormal outcomes.