Fungiform papillae are epithelial derived appendages that house the sensory organ of the gustatory system, the taste buds. Papillae, and the taste sensory stem cell domains within them, are patterned on the dorsal surface of the tongue in horizontal rows that extend along the anterior-posterior axis. The arrangement of fungiform papillae is well-conserved and provides an excellent system for investigating signaling interactions that drive the development of epithelialderived appendages. Using mouse genetics; in situ hybridization; in vitro organ explant cultures; and mathematical modeling, the data presented in this dissertation investigates interactions between the TGFβ, Wnt, and Sonic Hedgehog (SHH) signaling pathways, and their role in the specification and patterning of fungiform papillae in the tongue.
In Chapter One I provide: a review of the different strategies for pattern formation; background on tongue/fungiform papillae development; and a review of the Wnt, SHH, and TGFβ signaling pathways. In Chapter Two, interactions between Bone Morphogenetic Protein 7 (BMP7 - a member of the Transforming Growth Factor β (TGFβ) signaling superfamily), and its extracellular antagonist Follistatin are shown to be crucial in establishing and patterning the Sox2+ stem cell domains that will form fungiform papillae. Loss of Fst results in an expansion of Sox2 throughout the tongue epithelium, which leads to the aberrant development, patterning, and innervation of fungiform papillae. Chapter Three explores the role of BMP7 in taste papillae patterning, and tests experimentally and computationally, a 4-component network consisting of SHH, Wnt, BMP7, and FST that attempts to understand the mechanisms governing where fungiform papillae develop in the tongue. Data presented in this chapter suggest that a self-organizing Turing system patterns fungiform papillae in the lateral regions of the tongue, while a gradient of the diffusible morphogen, Wnt, imparts information that defines a midline boundary that remains free of papillae. Data presented in Appendix A supplements Chapter Three. In Appendix B, ActivinâB, a second TGFβ expressed in the tongue epithelium, and its role in the temporal dynamics of taste receptor cell maturation is investigated. Appendix C explores interactions between TGFβ and Notch signaling in modulating neurogenesis and gliogenesis in the olfactory epithelium.
|Advisor:||Calof, Anne L.|
|Commitee:||Anderson, Aileen, Lander, Arthur D., Smith, Martin, Waterman, Marian|
|School:||University of California, Irvine|
|Department:||Biomedical Sciences - Ph.D.|
|School Location:||United States -- California|
|Source:||DAI-B 73/04, Dissertation Abstracts International|
|Subjects:||Molecular biology, Neurosciences, Developmental biology|
|Keywords:||Sensory epithelia, Stem cells, Tissue patterning, Transforming growth factor beta, Wnt signaling|
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