Evidence suggests that stem cells recruit multiple signaling pathways to maintain their proliferative and uncommitted state. We have observed that this strategy is also operational in neural stem cells isolated from the embryonic retina and adult ciliary epithelium. In addition to EGF/FGF2-mediated receptor tyrosine kinase signaling, that have generally shown to promote the proliferation of neural stem cells, the signaling promoted by Delta/Serrate-Notch, Wnt-Frizzled, Sonic hedgehog-Patched and SCF-c-Kit pathways are important in the maintenance of retinal and CE neural stem cells/progenitors. One of the long-term goals of our lab is to decipher the cross talk between these disparate signaling pathways during the regulation of the ocular neural stem cells/progenitors. Towards this end we have shown cooperative interactions between c-Kit, Notch and Wnt signaling that keep these cells proliferating and uncommitted at the same time. We believe that signaling pathways that maintain ocular neural stem cells in proliferating and uncommitted state, also ensure cellular homeostasis. One of the target gene for cellular homeostasis is likely to be the multi-drug resistance protein, ABCG2, the molecular determinant of SP cells phenotypes of stem cells in general.
|Regulators of stem cells/progenitors maintenance||ABCG2 protein and SP cell phenotype of retinal stem cells/progenitors|