| Description |
The central nervous system is an amazingly complex structure. Understanding the process of lineage determination is one of the fundamental challenges facing developmental biologists. This dissertation is focused on deciphering the molecular mechanisms by which the wnt signaling pathway is involved in generating increasingly restricted neural progenitors from more multipotent precursors. Towards this aim, I took three approaches. First, I investigated the expression pattern of the wnt receptor, frizzled 9 (Mfz9), in mouse neural tube development. Specifically, I found that Mfz9 had an early, conserved expression pattern in the developing CNS when multipotent neuroepithelial precursors are becoming restricted to neuronal progenitors. Further, I demonstrated that Mfz9 protein was localized to these two progenitor pools and excluded from a glial restricted progenitor. This suggests that Mfz9 may have a role in neuroepithelial precursor to neuronal progenitor lineage determination. Second, using the Xenopus retina as a model system, I sought to determine when and where the Wnt/|3-catenin pathway was active during retinogenesis. I determined that the Wnt/p-catenin was active in proliferating retinal precursors and in the more restricted neural retinoblasts. Third, I sought to determine the role of Xenopus frizzled 5 (Xfz5) in retinogenesis which has an expression pattern restricted to the developing neural retina. I determined that Xfz5 is involved in the transition from the multipotent retinal precursor to the more restricted neural retinoblast. Knocking down Xfz5 function results in a dramatically reduced, but normal eye. This is likely due to a decrease in proliferation of neural retinoblasts. Further, inhibiting Xfz5 function results in a delay in the onset of both neurogenic and proneural genes in the neural retinoblasts. My data suggest that in the absence of Xfz5 function, the entire program in the initiation of the proliferating neural retinoblast is delayed. Collectively, these results enhance our understanding of lineage determination in the developing CNS, suggesting that wnt signaling may be important in the development of increasingly restricted progenitors. |
