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Title page for ETD etd-03252009-162556


Type of Document Dissertation
Author Zannino, Denise Allison
Author's Email Address dzannino2003@yahoo.com
URN etd-03252009-162556
Title Multiple roles for olig2 in the hindbrain: oligodendrocyte and abducens motor neuron specification and facial motor neuron migration
Degree PhD
Department Neuroscience
Advisory Committee
Advisor Name Title
David Miller Committee Chair
Bruce Appel Committee Member
Michael Cooper Committee Member
Stacey Huppert Committee Member
Keywords
  • Motor neurons -- Growth
  • Oligodendroglia
  • neural precursors
  • hindbrain
  • olig2
  • oligodendrocyte
  • cranial motor neurons
  • zebrafish
  • Spinal cord -- Growth
Date of Defense 2009-02-27
Availability unrestricted
Abstract
In the spinal cord, most oligodendrocytes, the myelinating cell type of the CNS, and motor neurons arise from common, ventral, olig2-expressing precursors called pMN cells. In the hindbrain, the degree to which motor neurons and oligodendrocytes share common origins and, consequently, are specified by similar molecular mechanisms is not clear. This ambiguity results, at least in part, from the fact that both oligodendrocyte progenitor cells (OPCs) and some motor neurons migrate, obscuring whether these cells have common or distinct origins. Therefore, we used zebrafish as a model system to investigate hindbrain motor neuron and oligodendrocyte development. We found, using cell specific markers, transgenic reporter lines and time-lapse microscopy, that a subset of OPCs and abducens motor neurons, which control eye movement, arise from common olig2-expressing precursors in rhombomeres (r) 5 and 6. To investigate the role of olig2, we reduced its function using translation-blocking morpholino oligonucleotides. This produced deficits of OPCs and abducens motor neurons, but not other motor neuron populations. However, we also found that facial motor neurons failed to complete their migration from r4 into r6 and r7. This raises the possibility that the olig2+ precursors provide a positional cue necessary for facial motor neuron migration. A better understanding of proper OPC and neuronal specification and migration in the hindbrain will bring increased insight to motor neuron disorders such as Mobius Syndrome and Duane Syndrome, which affect the facial and abducens motor neurons, respectively, as well as demyelinating disorders, such as Multiple Sclerosis.
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