Cell signaling in the third pharyngeal pouch
O'Neil, John David
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The third pharyngeal pouch is a columnar epithelium which is derived from the pharyngeal endoderm. In the mouse, it develops at roughly E9.0 and differentiates into the thymus and the parathyroids. At E11.5, the thymus and parathyroid domains of the pouch express the transcription factors Foxn1 and Gcm2 respectively. While thymus and parathyroid-specific domain markers, the mechanisms by which each domain is established are largely unknown. Here, we expand upon the current studies on the effects of sonic hedgehog (Shh), bone morphogenic protein (Bmp), and fibroblast growth factor (Fgf) signaling. We leverage several different approaches, including genetic manipulation by Cre-loxp technology and an ex vivo culture system to better understand the role Bmp, Fgf, and Shh signaling in in the patterning of the third pharyngeal pouch epithelium. Our study shows that Bmp4 and Fgf8 act opposite Shh in the pouch in order to inhibit parathyroid fate and activate thymus fate within the third pharyngeal pouch while Shh activates Tbx1, a known inhibitor of Foxn1 expression in the dorsal pouch. We also show that Bmp signaling is required for parathyroid fate, a result that parallels data from an earlier study in chick.