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The roles of Pbx and Meis TALE-class homeodomain transcription factors in vertebrate neural patterning Open Access

Descriptions

Other title
Subject/Keyword
pbx
neural
midbrain
engrailed
hox
zebrafish
segmentation
patterning
hindbrain
vision
development
tectum
retina
homeodomain
teashirt
transcription
TALE-class
neuron
meis
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Erickson, Timothy
Supervisor and department
Waskiewicz, Andrew (Biological Sciences)
Examining committee member and department
Allison, Ted (Biological Sciences)
Godbout, Roseline (Oncology)
Schuurmans, Carol (Biochemistry and Molecular Biology, University of Calgary)
Lehmann, Ordan (Ophthalmology)
Department
Department of Biological Sciences
Specialization

Date accepted
2010-08-26T14:57:21Z
Graduation date
2010-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
One of the major goals of developmental biology is to understand how specialized groups of cells arise from an initially unspecified cell population. The vertebrate hindbrain is transiently segmented along its anterior-posterior axis into lineage-restricted compartments called rhombomeres, making it an excellent model in which to study the genetic mechanisms of axial patterning. Hox homeodomain transcription factors (TF), in close partnership with the Pbx and Meis families of TALE-class homeodomain proteins, impart unique molecular identities to the hindbrain rhombomeres, thereby specifying functionally specialized neurons within each segment. The broad goals of this thesis are to clarify the roles of Meis1 and Tshz3b TFs in Hox-dependent hindbrain patterning, and to examine the Hox-independent roles of Pbx and Meis proteins in axial patterning of the visual system. While it is clear that Hox-Pbx-Meis complexes regulate hindbrain segmentation, the contributions of individual Meis proteins are not well understood. I have shown that Meis1-depleted embryos exhibit neuronal patterning defects, even though the hindbrain retains its segmental organization. This suggests that Meis1 is making important contributions to neuronal development downstream of rhombomeric specification. A zinc-finger TF called Teashirt (Tsh) cooperates with Hox-Pbx-Meis complexes to establish segmental identity in Drosophila, but this role not been tested in vertebrates. I found that overexpression of tshz3b produces segmentation defects reminiscent of Hox-Pbx-Meis loss of function phenotype, likely by acting as a transcriptional repressor. Thus, Tshz3b may be a negative regulator of Hox- dependent hindbrain patterning. Like the hindbrain, visual system function requires that positional information be correctly specified in the retina and midbrain. I found that zebrafish Pbx and Engrailed homeodomain TFs are biochemical DNA binding partners, and that this interaction is required to maintain the midbrain as a lineage- restricted compartment. Additionally, I show that Meis1 specifies positional information in both the retina and midbrain, thereby helping to organize the axonal connections between the eye and brain. Taken together, this thesis clarifies our understanding of Hox-dependent hindbrain patterning, and makes the claim that Pbx and Meis perform a general axial patterning function in anterior neural tissues such as the hindbrain, midbrain and retina.
Language
English
DOI
doi:10.7939/R38H0H
Rights
License granted by Timothy Erickson (timothye@ualberta.ca) on 2010-08-25T20:44:31Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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