Hox transcription factors have been implicated in many aspects of embryonic rostrocaudal (or anteroposterior) patterning. I have examined the roles of two members of this family, Hoxd10 and Hoxd11, in the development of the lumbosacral (LS) region of the embryonic chick spinal cord. Hoxd10 is expressed uniformly throughout the LS spinal cord at early stages of motoneuron development, but later restricted to subsets of motoneurons in rostral segments. In contrast, Hoxd11 is expressed exclusively in caudal LS segments. Data presented here from overexpression experiments provide evidence that Hoxd10 promotes the development of motoneurons of the lateral subdivision of the lateral motor column (LMCl). Motoneurons transfected with Hoxd10 were likely to acquire a molecular profile, position, and peripheral axonal trajectory consistent with an LMCl identity. In contrast, Hoxd11 suppresses LMCl formation, and imparts a caudal and medial identity upon motoneurons, most likely via repressive interactions with Hoxd10 and the retinoic acid synthetic enzyme RALDH2. To further elucidate the mechanisms governing these opposing actions, I have also created a hybrid protein in which the DNA-binding homeodomain of Hoxd10 is replaced with that of Hoxd11 (Hoxd10d11HD). Hoxd10d11HD, when expressed in LS segments, behaves in a manner similar to Hoxd11, and in direct opposition to Hoxd10, by suppressing the development of the LMCl. It is therefore likely that some of the functionally specific actions of Hoxd11 are governed by the properties of its homeodomain.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-07162009-102840 |
| Date | 13 August 2009 |
| Creators | Misra, Mala |
| Contributors | Joseph W. Yip, Laura E. Lillien, Michael P. Matise, Carl F. Lagenaur, Cynthia Lance-Jones, Deborah L. Chapman |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-07162009-102840/ |
| 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 University of Pittsburgh 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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