An Experimental Study On The Expression Of Wnt Signaling Molecules In Rat Brain And Their Role In The Proliferation And Differentiation Process Of Neural Stem Cells

Wnt signaling pathway plays a pivotal role in the embryonic development and tumorigenesis. It has been proved to regulate diverse processes including cell proliferation, cell fate specification, migration and polarity. β-catenin is a central and essential component of the canonical Wnt signaling pathway and acts downstream of the Wnts binding receptor Frz and LRP. Wnt signals activate this pathway and lead accumulation of β-catenin in the cytoplasm, β-catenin then enters the nucleus where it modulates gene expression through interacting with Tcf/Lef transcription factors. In the cytoplasm, β-catenin is mainly regulated by the so-callled "β-catenin destruction complex" formed by adenomatous polyposis coli protein (APC), Axin and glycogen-synthase kinase 3β (GSK3β). GSK-3β mediates phosphorylation of β-catenin and phosphorylated P-catenin is unstable. It is accepted that Wnt signals activate the pathway mainly by modulating this process.In the nervous system, it has been well documented that wnt genes are involved in the processes of neural tube and neural crest formation. In the past few years, Wnt proteins have also been proved not only playing a key role in the synaptogenesis but in the cortex pattern formation. However, most of the previous studies focused on Wnt genes themselves in the early development. Reports about the other downstream signaling components of canonical Wnt pathway such as APC, Gsk-3β in the development of CNS, especially in the process of postnatal development, are rare so far. Actually, it has been found that such signaling factors are not only involved in the neurogenesis, but also in the neural plasticity and some degenerative disorders as well. Nowadays, neural stem cells(NSCs) is a hot area in the developmental neurobiology, the mechanism of its proliferation and differentiation remains unclear. It is still debated about the roles of Wnt signaling molecules in the process of proliferation, differentiation as well as cell fate decision of NSCs, and how they function. From the observation of Wnt signaling factors knockout and adult brain tissue experiment, some researchers agree that activation of Wnt pathway promotes stem cell proliferation and...