| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
To determine whether GSK3 plays a role in medio-lateral patterning within the OC, multiple GSK3 antagonists were tested in vitro in cochlear explants. Inhibition of GSK3 leads to a dramatic increase in the size of the medial domain and a proportional decrease in the size of the lateral domain. Lineage tracing reveals that this shift occurs as a result of lateral cells adopting a medial cell fate. This is significantly different from the changes observed in response to activation of canonical Wnt signaling; an increase in the number of overall hair cells. We have demonstrated that BMP4, an inducer of the lateral OC domain, and its downstream targets are reduced following GSK3 inhibition and that ectopic BMP4 treatment partially rescues the shift in lateral to medial cell fate. This work will help to elucidate the molecular mechanisms that are necessary for patterning the OC along the medio-lateral axis.
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