RUI: Elucidating the signaling interactions that control spinal cord fate specification

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This project advances understanding of how cells in embryos interpret localized signaling cues to decide their fate, that is, the type of tissue to become. This complex problem is simplified by investigating a simple binary decision event: the specification of posterior neural precursor cells to become either hindbrain or spinal cord. This decision is controlled by three signaling molecules regulating the expression of one gene family. Because developmental signal interactions are conserved across organisms, this research will expand our knowledge of signal interactions in the nervous system specifically, while also providing a foundational framework to understand vertebrate head-trunk evolution more generally. This work will have broad intellectual implications in neurobiology, developmental biology, and evolutionary biology. The project will also support the training of undergraduate students, fostering inquiry-based research essential to developing the skills needed in a thriving US scientific workforce.A remarkably small number of signaling factors specify a large number of cell fates during the development of vertebrate tissues, and the nervous system is no exception. A striking example occurs in the caudal neural plate, where inputs of the signaling molecules FGF, Wnt and Retinoic Acid are required to specify which portion of the tissue will become spinal cord and not hindbrain. Previous studies have shown that FGF-Wnt, FGF-RA and Wnt-RA all contribute to regulation of the spinal cord specification gene cdx4. This project will focus on determining the individual and collective contribution of these three signals to spinal cord specification. By determining these interactions, the project will produce a detailed map of the signaling networks coordinating hindbrain-spinal cord specification, an important step for further analysis of nervous system development and evolutionThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.