The Resource Examining the role of Gbx1 in spinal cord development and its contribution to mammalian locomotion, by Desirè M. Buckley

Examining the role of Gbx1 in spinal cord development and its contribution to mammalian locomotion, by Desirè M. Buckley

Label
Examining the role of Gbx1 in spinal cord development and its contribution to mammalian locomotion
Title
Examining the role of Gbx1 in spinal cord development and its contribution to mammalian locomotion
Statement of responsibility
by Desirè M. Buckley
Title variation
Examining the role of gastrulation brain homeobox one in spinal cord development and its contribution to mammalian locomotion
Creator
Contributor
Author
Thesis advisor
Subject
Genre
Language
eng
Summary
Animals explore their environment through locomotion. Motion is generated by the activity of sensorimotor circuits formed in the spinal cord during embryogenesis, which are further refined postnatally. These circuits are composed of spinal sensory interneurons and motor neurons, which integrate proprioceptive somatosensation mediated by peripheral sensory neurons. Together, peripheral proprioceptive sensory neurons and spinal motor neurons constitute the simplest sensorimotor circuit controlling locomotion, the monosynaptic stretch reflex circuit. Transcription factors expressed during embryogenesis play a critical role in the assembly of sensorimotor circuits that facilitate locomotive behaviors. Gbx1 is a member of the murine Gbx family of homeodomain-containing transcription factors. It is dynamically expressed in neuronal populations in the dorsal and ventral spinal cord throughout embryonic development. In the dorsal spinal cord, Gbx1 is required to maintain a subset of inhibitory PAX2+ interneurons. It is also required for normal locomotor output of the hindlimbs. The other Gbx family member, Gbx2, is also expressed in spinal neuron populations during embryonic development. However, its function has been best characterized in establishment and development of the midhindbrain boundary and anterior hindbrain. The studies presented in this dissertation provide the first functional analysis for Gbx1 in the spinal cord and were designed to examine the role of Gbx1 in locomotion. To examine the role of Gbx1 in the developing spinal cord, we generated mice carrying a loss-of-function allele for Gbx1 (Gbx1-/- ). By postnatal day 15, Gbx1-/- mice begin to display a gross locomotive defect that specifically affects hindlimb gait. Molecular analysis of mutant embryos revealed premature termination of 1a afferents, axons of proprioceptive sensory neurons, in the dorsal spinal cord. In addition, a subset of motor neurons in the ventral spinal cord is lost, at mid-embryonic stages. Both observations persisted at postnatal stages. The loss of motor neurons prompted us to investigate the underlying mechanism, which we identified as apoptosis-mediated cell death. Notably, the cell types affected by loss of Gbx1 are highly involved in controlling locomotor output. We also briefly assessed possible interaction of Gbx1 with its family member Gbx2 in spinal neuron development using Gbx1-/- ; Gbx2 -/- double knockout mutant embryos. Genetic inactivation of Gbx family members independently, result in significant reduction of PAX2+ cells in the superficial layers (laminae I-II) of the dorsal spinal cord. However, this phenotype was not exacerbated in double knockout embryos. Together these data suggest that Gbx family members are required to maintain PAX2 cell fate in the dorsal spinal cord, but not functionally redundant for this shared function. Data herein demonstrate a requirement for Gbx1 in normal locomotor output. Additionally, identification of the mechanism resulting in death of motor neurons has revealed a novel requirement for Gbx1 in spinal motor neuron survival. Collectively, data presented herein support a model for involvement of Gbx1 in development of monosynaptic stretch reflex circuit components
Cataloging source
MUU
http://library.link/vocab/creatorName
Buckley, Desirè M
Degree
PhD
Dissertation note
Thesis
Dissertation year
2015.
Government publication
government publication of a state province territory dependency etc
Granting institution
University of Missouri--Columbia
Illustrations
illustrations
Index
no index present
Literary form
non fiction
Nature of contents
  • dictionaries
  • bibliography
  • theses
http://library.link/vocab/relatedWorkOrContributorName
Waters, Samuel T.
http://library.link/vocab/subjectName
  • Spinal cord
  • Homeobox genes
  • Transcription factors
Label
Examining the role of Gbx1 in spinal cord development and its contribution to mammalian locomotion, by Desirè M. Buckley
Instantiates
Publication
Note
  • "A Dissertation Presented to The Faculty of the Graduate At the University of Missouri In Partial Fulfillment Of the Requirements for the Degree Doctor of Philosophy."
  • Dissertation advisor: Samuel T. Waters
  • Includes vita
Bibliography note
Includes bibliographical references (pages 156-170)
Carrier category
online resource
Carrier category code
  • cr
Carrier MARC source
rdacarrier
Content category
text
Content type code
  • txt
Content type MARC source
rdacontent
Control code
958846120
Extent
1 online resource (ix, 171 pages)
Form of item
online
Media category
computer
Media MARC source
rdamedia
Media type code
  • c
Other physical details
illustrations (chiefly color)
Specific material designation
remote
System control number
(OCoLC)958846120
Label
Examining the role of Gbx1 in spinal cord development and its contribution to mammalian locomotion, by Desirè M. Buckley
Publication
Note
  • "A Dissertation Presented to The Faculty of the Graduate At the University of Missouri In Partial Fulfillment Of the Requirements for the Degree Doctor of Philosophy."
  • Dissertation advisor: Samuel T. Waters
  • Includes vita
Bibliography note
Includes bibliographical references (pages 156-170)
Carrier category
online resource
Carrier category code
  • cr
Carrier MARC source
rdacarrier
Content category
text
Content type code
  • txt
Content type MARC source
rdacontent
Control code
958846120
Extent
1 online resource (ix, 171 pages)
Form of item
online
Media category
computer
Media MARC source
rdamedia
Media type code
  • c
Other physical details
illustrations (chiefly color)
Specific material designation
remote
System control number
(OCoLC)958846120

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