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Abstract
The thymus and parathyroid have different functions and locations in the adult body. Despite these differences, both organs arise from a common primordium in the embryo: the third pharyngeal pouch (3rd PP). A longstanding question is how cells in the 3rd PP are specified into the thymus or parathyroid. Two transcription factors, FOXN1 and GCM2, are essential for the survival of the thymus and parathyroid, respectively, and serve as early markers of each organ. However, these transcription factors are not the specifiers of the thymus or PT, and the specifiers remain unknown. An additional unknown mechanism of thymus and PT cell fate specification is the signals driving each fate from the surrounding mesenchyme, pharyngeal endoderm, and surface ectoderm. To identify candidate transcription factors specifying the thymus and PT, as well as extracellular signals driving such specifiers, I performed scRNA-seq on the 3rd PP and its surrounding tissues at two timepoints spanning thymus and parathyroid cell fate specification (E10.25-11.25). Using these data, I identified Vgll2 and Sox2 as candidate genes acting cell autonomously to control 3rd PP cell fates. I also identified Wnt4/6 as a candidate signal driving the thymus cell fate, with the WNT inhibitor, Sfpr2 as a candidate permissive signal for the parathyroid cell fate. A second part of my project is to characterize the cell cycle gating of the SHH response. Using the FUCCI cell cycle reporter system, I show that cells in G2/M phases of the cell cycle are able to respond to SHH at a higher frequency. This study provides new information into how the thymus and parathyroid cell fates are specified, and how cells are able to perceive their environment throughout the cell cycle.