Receptor kinase signal integration in stem cell maintenance

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Project Summary The long term goal of the proposed research is to decipher how cell to cell signaling networks control stem cell maintenance. Because stem cell activity is critical to human development, and a current goal of the field is to harness the properties of stem cells for disease treatment, an understanding of the molecular networks controlling stem cell function is critical for diverse public health challenges. We have chosen a highly tractable model plant system, Arabidopsis thaliana, to take a multi-level approach to dissect the receptor kinase pathways that control shoot stem cell proliferation. Arabidopsis is easy to transform, mutagenize, and there is a wealth of mutants and transgenic lines that affect stem cell function, all acquired during decades of study. In addition, the stem cell niche in the shoot is easily visualized, allowing living stem cells to be imaged at cellular and sub-cellular levels. The proposal will support a series of projects that collectively aim to comprehensively understand the function of receptor signaling in stem cell regulation. The projects will identify the transcriptional regulators that act downstream of receptor activation, tie their function to signaling cascades, and identify the suite of transcriptional outputs they regulate. The proposal will also define the mechanism of receptor activation and complex formation at the plasma membrane and elucidate the signaling components that act as intermediates through a combination of novel genetic and biochemistry approaches. The project will assess how stem cell network components have diversified and been co-opted into new developmental modules outside of the shoot stem cell niche. Lastly, the project will take a broad evolutionary approach to assess how stem cell networks have been altered by evolution and domestication to shape form and function. The project will last five years, but will impact the direction of the lab beyond the scope of the proposed research. The projects will train scientists at the post-doctoral, graduate and undergraduate levels. This work will benefit from collaboration with several expert groups using different model systems with the aim of amplifying and diversifying data sets, and exchanging skill sets. Ultimately, the projects aim to define network architecture and specificity at a level that allows the creation of synthetic pathways with the potential to alter plant growth and be deployed in heterologous systems, potentially including therapeutic applications.