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Hoxd10 and Hoxd11 regulate motor column patterning in the lumbosacral spinal cord

Misra, Mala (2009) Hoxd10 and Hoxd11 regulate motor column patterning in the lumbosacral spinal cord. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLagenaur, Carl Flagenaur@pitt.eduLAGENAUR
Committee MemberLance-Jones, Cynthiaclancej@pitt.eduCLANCEJ
Committee MemberChapman, Deborah Ldlc7@pitt.eduDLC7
Committee MemberYip, Joseph Wjyip@pitt.eduJYIP
Committee MemberLillien, Laura Elillien@pitt.eduLILLIEN
Committee MemberMatise, Michael
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:, etd-07162009-102840
Date Deposited: 10 Nov 2011 19:51
Last Modified: 15 Nov 2016 13:46


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