The existence of anatomical differences along the left-right (L-R) axis in the brain and visceral organs is an evolutionarily conserved feature of the vertebrate lineage. Although much is known about the molecular pathways that lead to the development of visceral organ asymmetry, we are just starting to understand the molecular processes that lead to the development of brain laterality. The zebrafish epithalamus, which includes the pineal organ and a left sided accessory organ called the parapineal organ, offers a powerful model to study the events leading to the generation of brain asymmetry. A chemical mutagenesis screen was performed to identify mutants that disrupt laterality in the epithalamus. The from beyond (fby)/tbx2b mutation causes a brain-specific defect in laterality including a decrease in the total number of specified parapineal cells and an inability of parapineal cells to migrate to the left of the pineal organ. Time-lapse imaging of wild-type parapineal cells show several cells emerging from the pineal complex anlage and migrating as a group in a leftward direction. Similar time-lapse imaging of fby mutants shows that this leftward migration does not occur. Further, ablation of some parapineal cells in wild-type embryos show that reduced cell number does not prevent migration of the remaining cells in fby mutants. Characterization of a hypomorphic allele of tbx2b, lots-of-rods (lor), further supports the hypothesis that specification and migration defects found in tbx2b mutants are separable events that require different doses of tbx2b. Currently, the transcriptional regulators of tbx2b in the pineal complex are unknown; however a previous report had suggested that Floating Head (flh) protein controls tbx2b transcription in the epithalamus. Our studies suggest that this is not the case, and that Flh and Tbx2b act in parallel pathways. Fate mapping, in conjunction with efforts to identify upstream regulators and downstream targets of tbx2b activity in the developing pineal complex, will help determine the mechanism of parapineal organ formation.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03082009-174018 |
| Date | 13 March 2009 |
| Creators | Snelson, Corey Deanne |
| Contributors | Joshua Gamse, Christopher Wright, Laurence Zweibel, Lilianna Solnica-Krezel, Jason Jessen |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu//available/etd-03082009-174018/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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