| Budget Amount *help |
¥72,600,000 (Direct Cost: ¥72,600,000)
Fiscal Year 2004: ¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 2003: ¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 2002: ¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 2001: ¥19,800,000 (Direct Cost: ¥19,800,000)
|
|---|
| Research Abstract |
We have investigated how Notch signaling and musashi that has been suggested to potentiate Notch signaling activity by translationally inhibiting Notch antagonist, Numb (Imai et al., 2001), control the self-renewal and/or differentiation of neural stem cells. In addition, we have developed a system in which ES cells could be efficiently induced to differentiate into dopaminergicneuronsormotorneurons (Yoshizaki et al.2004 ; Okada et al.,2004) andatechniquetoisolateneuralstemcells that exist in ventral mesencephalon and differentiate them into TH (Tyrosine Hydoxylase) positive dopaminergicneurons, using nestin promoter EGFP Tg animal and FACS sorting (Sawamoto et al., 2001).
We first performed genetic analyses of Drosophila musashi (d-musashi) andfoundthatd-musashicouldinhibitTramtrack, which we found one of the targets of dMusashi, only in the one daughter cells where Notch signaling are not activated, and could not do so in the other daughter cells where Notch signaling are activated, t
… More
hereby making two daughter cells differentiate into neurons or glia, respectively (Okabe et al., 2001). We extended the analysis to mammalian d-Musashi homolog, m-musashi and found that Numb is a putative downstream target of m-musashi. In the meantime, we have also performed phenotypic analyses of m-musashi 1/2 knockout mice and demonstrated that m-musashiisrequiredfortheneural stem cells to selfrenew (Sakakibara et al., 2002). We hypothesized that m-musashi might promote selfrenewal activity of neural stem cells by potentiating the Notch signaling activity through translational inhibition of Numb. To further establish the link between the potentiation of selfrenewal activity of neural stem cells and the modulation of Notch signaling activity, both are mediated by m-musashi, wehave developedthetechniquewhichenablesustomonitorthe activity of Notch signaling and thereby examine the relationship between Musashi and the activity of Notch (Tokunaga et al., 2004 ; Koyama et al., in preparation). Less
|
