EMORY UNIVERSITY
Grant: $199,950 - National Institutes of Health - Aug. 11, 2009
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Award Description: Cilia play well-established roles in motility and cell signaling in the mammalian nervous system. Our current understanding of how the neuroepithelium gives rise to specific neurons while maintaining a progenitor cell population has been focused on defining the genes and relevant regulatory networks. Consequently we do not yet have a handle on the cellular behavior underlying these distinct cell fate choices. Here we aim to determine the correlation of signaling response and formation of cilia in neuroepithelial progenitors. We propose that normally when a progenitor divides, one daughter responds to Shh signaling and differentiates while the other retains its progenitor state. However, in a mouse mutant we study, the lack of Arl13b results in precocious differentiation of the progenitor cells as both daughter cells differentiate due to constitutive Shh activity. This model implies that the cell division of a progenitor cell is inherently asymmetric with respect to its ability to respond to Shh and since Arl13b function is required in cilia we suggest that this asymmetry may be related to cilia formation in the daughter cells. This implies that the behavior of cells may play an important role in protecting stem and progenitor cell niches in vivo. Using live imaging and time-lapse confocal microscopy, we will monitor single cell divisions in the developing neuroepithelium of wild type and Arl13b mutant cells and observe Shh response and cilia formation via fluorescent reporters. These experiments will reveal a fundamental difference between the daughter cells that result from a cell division. In doing so, we will gain not only a clearer idea of where Arl13b is required, but mechanistic picture of how cells in a stem cell niche can be maintained and evade the signaling pathways to which they are exposed.
Project Description: This proposal will study the mechanism underlying a mutant mouse phenotype we observe. We have purchased a workstation and the associated software with which to analyze the data. We are in the process of hiring a new postdoctoral fellow to perform the work.
Infrastructure Description: N/A
Jobs Summary: We have advertised a new postdoctoral fellow position and have selected qualified candidates to be interviewed. This person will be responsible for performing the experiments as described within this proposal. Thus, this postdoctoral fellow will perform the mouse breedings, dissections, viral infections and imaging central to this proposal. The postdoctoral fellow will be mentored by Dr. Caspary who will aid in data interpretation, presentation and manuscript preparation. (Total jobs reported: 0)
Project Status: Less Than 50% Completed
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