| Budget Amount *help |
¥44,460,000 (Direct Cost: ¥34,200,000、Indirect Cost: ¥10,260,000)
Fiscal Year 2023: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2022: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2021: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2020: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Outline of Final Research Achievements |
This study aimed to elucidate the force generation mechanism that propels nuclear migration in crowded neural tissue in the developing cerebellar cortex. We demonstrated that the mechanosensor PIEZO1 is activated by the increase in plasma membrane tension in crowded tissue, inducing actomyosin contraction in the posterior plasma membrane via the PKC-Ezrin axis. On the other hand, the nucleus-motor adaptor Nesprin2 generates continuous bidirectional movements along the perinuclear microtubules that move forward in migrating neurons. The nucleus frequently undergoes DNA damage by mechanical stress during neuronal migration in the crowded neural tissue. The DNA double strand breaks (DSBs) are rapidly repaired by the non-homologous end-joining (NHEJ) pathway. We generated conditional deletion mutant of Ligase IV and found that the failure in the NHEJ pathway causes the accumulation of unrepaired DSBs into adulthood, leading to progressive motor deficiency in later life.
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