| Project/Area Number |
13854027
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Developmental biology
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| Research Institution | RIKEN (2002-2005)
Tohoku University (2001) |
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Principal Investigator |
MATSUZAKI Fumio RIKEN, Cell Asymmetry, Group Director, 非対称細胞分裂研究グループ, グループディレクター (10173824)
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| Co-Investigator(Kenkyū-buntansha) |
IZUMI Yasushi RIKEN, Cell Asymmetry, Special Postdoctral Fellow, 非対称細胞分裂研究グループ, 基礎科学特別研究員 (10373268)
布施 直之 独立行政法人理化学研究所, 非対称細胞分裂研究グループ, 研究員 (80321983)
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| Project Period (FY) |
2001 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥121,810,000 (Direct Cost: ¥93,700,000、Indirect Cost: ¥28,110,000)
Fiscal Year 2005: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
Fiscal Year 2004: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2003: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2002: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2001: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
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| Keywords | neural stem cell / asymmetric division / cell polarity / G-protein / aPKC / epithelial cell / PKC / miranda / 多様性 / 非対称性 / prospero / Miranda |
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| Research Abstract |
Drosophila neuroblasts undergo typical asymmetric divisions, during which cell-fate determinants localize to the basal cortex, mitotic spindles orient along the apical-basal axis, and unequal-sized daughter cells appear. We have carried out a large scale genetic screen to identify mutants defective in the neuroblasts asymmetric division.
1.Among several mutants showing novel phenotypes, two mutations disrupt cell size asymmetry between the daughters but not asymmetric localization of the determinants such as Miranda. These genes encode G□13F and G□1 subunits of heterotrimeric G proteins, respectively, which form a cortical complex. In the wild type neuroblasts, the basal spindle half is smaller than the apical one, forming the smaller basal daughter. In contrast, elimination of G□□ results in a large symmetric spindle in random orientations and causes division into nearly equal-sized cell, suggesting a critical role of G□□in asymmetric spindle organization in neuroblasts.
2.We also asked
… More
how spindle orientation is regulated by examining dividing epithelial cells and neuroblasts in those mutants ; it has been unclear because spindle orientation in neuroblasts is randomized by depleting any one of those components. It turned out that the spindle always points toward Pins location when it localizes asymmetrically, suggesting that Pines predominantly regulates spindle orientation. We are currently searching molecules acting with Pins to orient the mitotic spindle. By both genetic and biochemical screens, we identified Drosophila Mushroom body defect (Mud) as an essential factor in receptor-independent G protein signalling (Gαi and Pins) responsible for regulating spindle orientation in both cell types. Based on our study, we propose that Drosophila Mud, vertebrate NuMA and C.elegans Lin-5 play comparable roles in receptor-independent G-protein signalling and that these molecules, together with Pins GoLoco proteins and Gαi, constitute an essential part of a general mechanism regulating the mitotic spindle through interaction with astral microtubules. Less
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