Misra, Mala
(2009)
Hoxd10 and Hoxd11 regulate motor column patterning in the lumbosacral spinal cord.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
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.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
13 August 2009 |
| Date Type: |
Completion |
| Defense Date: |
29 June 2009 |
| Approval Date: |
13 August 2009 |
| Submission Date: |
16 July 2009 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Neurobiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Hox genes; motoneuron; developmental biology; chick; spinal cord |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-07162009-102840/, etd-07162009-102840 |
| Date Deposited: |
10 Nov 2011 19:51 |
| Last Modified: |
15 Nov 2016 13:46 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8405 |
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