Investigating Wnt/ss-catenin signaling in stem cells and progenitors of the developing and adult mouse brain
- In order for a tissue to be properly sized and patterned, enormous care must be taken to ensure that cell proliferation and differentiation are tightly regulated. The embryonic brain must execute a temporally and spatially defined developmental scheme, resulting in the production of millions of cells of multiple lineages. These cells and their resultant functional architecture must be maintained in the homeostatic adult mouse brain. These processes are in part controlled by external signaling factors, which include Wnts, and their transcriptional programs. However, the degree to which and exact mechanisms by which cell fate choices--including self-renewal, proliferation, and differentiation--are controlled by Wnt/ss-catenin signaling are unknown. Here, I describe studies to investigate these questions. First, I show the identification of a novel target of Wnt/sscatenin signaling, Pou6f1, which mediates neural differentiation and proliferation in embryonic neural progenitor cells. Next, I illustrate the use of a lineage tracing approach using a Wnt/ss-catenin target gene, Axin2, to identify and trace sites of Wnt/ss-catenin responsiveness in the developing and adult mouse brain and central nervous system. Using this same Axin2CreERT2 mouse, I describe the functional consequences of loss of sscatenin from Axin2-expressing cells. Axin2CreERT2 labels numerous radial glial cell populations throughout the central nervous system, three of which serve as functional stem/progenitor populations. Loss of ss-catenin from adult Axin2+ populations results in tissue architecture defects and increased proliferation, presumably because Wnt serves as a self-renewal signal. These studies demonstrate the importance of Wnt/ss-catenin signaling for mediating multiple cell fate choices during the development and homeostasis of the mouse central nervous system, and suggest mechanisms by which neural stem/progenitor populations could be manipulated for therapeutic outcomes.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|Bowman, Angela Nicole
|Stanford University, Department of Developmental Biology.
|Nusse, Roel, 1950-
|Nusse, Roel, 1950-
|Statement of responsibility
|Angela N. Bowman.
|Submitted to the Department of Developmental Biology.
|Ph.D. Stanford University 2012
- © 2012 by Angela Nicole Bowman
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