JNK1 and JNK2 are ubiquitously expressed, while JNK3 is restricted to the brain, testes, and heart

population and its usefulness as a biomarker. In this work we focused our assessments of the effects of the soluble treatments on the number of Hes3+ cells. We did so for a number of reasons. First, the Hes3 gene itself is regulated by the treatments used here. The Notch ligand Delta4, for example, through a non-canonical pathway that includes the fast activation of several kinases and Endogenous Hes3+ Cells in the Adult Hippocampus subsequent phosphorylation of STAT3 on the serine residue, leads to transcription of the Hes3 gene. Therefore, Hes3+ cell numbers are a measure which is directly relevant to the treatments performed. Second, Hes3+ cells represent a subpopulation of Sox2+ cells . Sox2 is a very useful marker of immature cells in the adult brain but its expression is not confined to these cells. For example, Sox2 expression can be Vatalanib biological activity observed in reactive astrocytes in the area of gliosis induced by injury; in contrast, Hes3 is not expressed in areas of gliosis induced by a stab wound. Although the percentage of Hes3+ cells that are stem cells or progenitor cells is not yet determined, Hes3 assessments provide a more specific output than the broader, Sox2+ cell population. This may explain the more potent effects observed in the Hes3+/Sox2+ cell population in comparison to the total Sox2+ cell population. Third, Hes3 measurements offer a distinct advantage: Hes3 expression is maintained even in quiescent states, allowing the identification of immature cells in both the active and dormant states. The intracellular localization of Hes3 can vary significantly depending on state. In cultured neural stem cells, cells exhibit both nuclear and cytoplasmic Hes3 localization. When bFGF is withdrawn and the differentiation process starts, Hes3 expression becomes exclusively cytoplasmic and eventually disappears altogether. In the unchallenged adult brain, most Hes3+ cells exhibit exclusively cytoplasmic Hes3 localization, whereas cytoplasmic and nuclear Hes3 can be observed when cells from these regions are placed in cultured and stimulated with bFGF. 7 Endogenous Hes3+ Cells in the Adult Hippocampus The choice of soluble treatments for this work was based on our previous elucidation of the signals that regulate Hes3 expression and Hes3+ cell numbers. Hes3+ cells express a variety of receptors which render them sensitive to stimuli that regulate Hes3, including Fibroblast Growth Factor receptors, Notch receptors, Tie2 receptors, and the insulin receptor. We have previously shown that the Tie2 receptor is expressed on Sox2+ cells in the hilus of the hippocampus, suggesting that the direct target of these soluble factors in vivo are the neural precursor cells themselves. Both experimental paradigms presented here showed fast and potent increases in the number of Hes3+ cells. In addition, in both models we observed the largest effect in the hilus of the dentate gyrus. A quantitative difference between the two paradigms was that in the adult rat, the effects in the hilus were particularly prominent. This difference could be due to species differences, brain size differences, and the fact that in mice we used a simplified combination of treatments. A qualitative difference we observed was that in the rat, Sox2+ cells in the hilus co-expressed Hes3, whereas Sox2+ cells in the subgranular zone did not express Hes3. In contrast, in the mouse, Hes3+/Sox2+ cells are observed throughout the hippocampal areas. Our results raise the possibility that th