MULTIPLE ROLES FOR OLIG2 IN THE HINDBRAIN: OLIGODENDROCYTE AND ABDUCENS MOTOR NEURON SPECIFICATION AND FACIAL MOTOR NEURON MIGRATION
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...
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ndltd-VANDERBILT-oai-VANDERBILTETD-etd-03252009-1625562013-01-08T17:16:27Z MULTIPLE ROLES FOR OLIG2 IN THE HINDBRAIN: OLIGODENDROCYTE AND ABDUCENS MOTOR NEURON SPECIFICATION AND FACIAL MOTOR NEURON MIGRATION Zannino, Denise Allison Neuroscience 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. David Miller Michael Cooper Stacey Huppert Bruce Appel VANDERBILT 2009-04-01 text application/pdf http://etd.library.vanderbilt.edu//available/etd-03252009-162556/ http://etd.library.vanderbilt.edu//available/etd-03252009-162556/ en 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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Neuroscience Zannino, Denise Allison MULTIPLE ROLES FOR OLIG2 IN THE HINDBRAIN: OLIGODENDROCYTE AND ABDUCENS MOTOR NEURON SPECIFICATION AND FACIAL MOTOR NEURON MIGRATION |
description |
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. |
author2 |
David Miller |
author_facet |
David Miller Zannino, Denise Allison |
author |
Zannino, Denise Allison |
author_sort |
Zannino, Denise Allison |
title |
MULTIPLE ROLES FOR OLIG2 IN THE HINDBRAIN: OLIGODENDROCYTE AND ABDUCENS MOTOR NEURON SPECIFICATION AND FACIAL MOTOR NEURON MIGRATION |
title_short |
MULTIPLE ROLES FOR OLIG2 IN THE HINDBRAIN: OLIGODENDROCYTE AND ABDUCENS MOTOR NEURON SPECIFICATION AND FACIAL MOTOR NEURON MIGRATION |
title_full |
MULTIPLE ROLES FOR OLIG2 IN THE HINDBRAIN: OLIGODENDROCYTE AND ABDUCENS MOTOR NEURON SPECIFICATION AND FACIAL MOTOR NEURON MIGRATION |
title_fullStr |
MULTIPLE ROLES FOR OLIG2 IN THE HINDBRAIN: OLIGODENDROCYTE AND ABDUCENS MOTOR NEURON SPECIFICATION AND FACIAL MOTOR NEURON MIGRATION |
title_full_unstemmed |
MULTIPLE ROLES FOR OLIG2 IN THE HINDBRAIN: OLIGODENDROCYTE AND ABDUCENS MOTOR NEURON SPECIFICATION AND FACIAL MOTOR NEURON MIGRATION |
title_sort |
multiple roles for olig2 in the hindbrain: oligodendrocyte and abducens motor neuron specification and facial motor neuron migration |
publisher |
VANDERBILT |
publishDate |
2009 |
url |
http://etd.library.vanderbilt.edu//available/etd-03252009-162556/ |
work_keys_str_mv |
AT zanninodeniseallison multiplerolesforolig2inthehindbrainoligodendrocyteandabducensmotorneuronspecificationandfacialmotorneuronmigration |
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1716533306072236032 |