Left-Right asymmetry of the CNS is a highly conserved feature across vertebrate classes. Asymmetry is manifest at the levels of function and connectivity. But the neural correlates of these asymmetries and their developmental underpinnings are just beginning to be explored. The zebrafish habenular nuclei have functional as well as neuronal asymmetries and offer a molecularly manipulable and highly visualizable model to studying the cellular and developmental origins of CNS left-right asymmetry. Here I report an evolving developmental network that regulates the timing of habenular neurogenesis. This network involved environmental and endocrine cues (light and melatonin), morphogenetic pathways (FGF and Nodal) and several neurogenic genes (dbx1b, lhx9, kip2 and her6). These components act as a temporal neurogenic gate, dictating the onset of neurogenesis. This neurogenic gate is regulated asymmetrically acting first in the left habenula driving earlier neurogenesis there and impacts neuronal cell type specification. Together these findings deepen our understanding of the molecular mechanisms that drive neural fate specification and how these components can give rise to left-right asymmetry in the CNS.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-08042014-210109 |
| Date | 21 August 2014 |
| Creators | Dean, Benjamin Jurrien |
| Contributors | Charles C. Hong, Joshua T. Gamse, Douglas G. McMahon, David M. Miller III |
| 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-08042014-210109/ |
| 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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