Genetic Approaches to Understand the Timing of Gene Expression and Lineage Allocation in the Mouse Auditory System

Brown, Stephen D.

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Year:: 2011
Contributor:: Brown, Stephen D (creator); Zervas, Mark (Director); Freiman, Richard (Reader); Johnson, Mark (Reader); Fallon, Justin (Reader); Oliver, Douglas (Reader); Brown University. BIOMED: Molecular Biology, Cell Biology, and Biochemistry (sponsor)
Genre:: theses
Subject:: development; genetic inducible fate mapping; lineage; cell fate; auditory system; Economic development; Cell determination; Ear; Cochlear nucleus; Inferior colliculus
Extent:: xi, 171 p.
DOI: https://doi.org/10.7301/Z0C827J2

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Abstract:: Vital to the function of any organ system is the proper specification and distribution of cell types during development. This is especially true for the human nervous system, where hundreds of billions of cells are distributed throughout the body. Aside from generating correct cell types in developing tissues, the nervous system forms precise connections to coordinate and control a diverse array of systems. Deciphering the genetic and molecular events which mediate these processes is of fundamental importance in understanding how the complex interactions are established during development. Genetic approaches in the mouse model system have allowed for the investigation of developmental processes that link mechanisms of early gene expression and regulation with the emergence of unique cell types. The auditory system in mammals is an excellent example of multiple anatomical regions that work cooperatively to transduce and integrate information central to hearing. Notably, the gene Wnt1 is expressed in the primordia of two critical auditory centers, the cochlear nucleus of the hindbrain and inferior colliculus of the midbrain. Through a genetic inducible fate mapping approach, we demonstrate the relationship between the timing of Wnt1 expression in progenitors and the terminal fate and distribution of auditory neurons. In addition, we used mutant analysis to investigate the functional requirement of Wnt1 in auditory system development. Our results provide evidence for two models of how Wnt1 expression differentially affects the development of the cochlear nucleus and inferior colliculus, and that Wnt1 is required for a subset of auditory domains. Finally, a novel transgenic strategy for the in vivo assessment of genetic lineages is presented. This transgene was designed to provide the conditional and selective enrichment of iron-based contrast agents to genetically defined cell populations thereby allowing their direct imaging in vivo by magnetic resonance imaging (MRI). Utilizing this transgene in genetic fate mapping studies could further our understanding of how tissues are assembled in three-dimensions over time, or how cell populations change during the course of disease.
Notes:: Thesis (Ph.D. -- Brown University (2011)

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Brown, Stephen D., "Genetic Approaches to Understand the Timing of Gene Expression and Lineage Allocation in the Mouse Auditory System" (2011). Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z0C827J2

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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations

Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department.
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