Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp010c483m608
 Title: The relationship between the primary cilium, the cell cycle and Sonic hedgehog signaling Authors: Oyer, Halley Mellor Advisors: Eggenschwiler, Jonathan TDevenport, Danelle Contributors: Molecular Biology Department Subjects: Cellular biologyDevelopmental biology Issue Date: 2014 Publisher: Princeton, NJ : Princeton University Abstract: The Sonic hedgehog signaling pathway is used pre- and postnatally throughout mammalian growth and development to pattern many different tissues. A primary cilium is required for Shh signaling, and its presence is closely linked to cell cycle progression, but this structure has never been shown to be sufficient to provide signaling competency. We developed an in vitro technique for observing Shh pathway activation, cilia presence and cell cycle status on a per-cell basis. When the cell cycle is manipulated using chemical arresting agents, the cilia frequency increases above the baseline observed in proliferating cells, but this increase does not impart an increased ability of cells to respond to Shh pathway activation measured by transcription of the target genes Gli1 and Ptch1. The variation between Shh pathway activation rates is due to cells arresting at a time when they are not competent to respond to Shh pathway activation. By using proliferating FUCCI cells, we have shown that cilia frequency and Shh pathway activation vary throughout the cell cycle. The differential Shh competency as observed by observation of Ptch1 transcripts is not simply due to cilia maturity, but is conferred by an unidentified cell cycle-dependent factor. A similar relationship between cell cycle phase and the ability to transcribe Ptch1 is observed in vivo. This cell cycle phase restriction acts to provide an additional layer of regulation for the powerful Shh signaling cascade. URI: http://arks.princeton.edu/ark:/88435/dsp010c483m608 Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog Type of Material: Academic dissertations (Ph.D.) Language: en Appears in Collections: Molecular Biology

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