| Project/Area Number |
23390064
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
HIROSHI Shibuya 東京医科歯科大学, 難治疾患研究所, 教授 (30261324)
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| Co-Investigator(Renkei-kenkyūsha) |
SATO Atsushi 東京医科歯科大学, 難治疾患研究所, 助教 (30451925)
GOTO Toshiyasu 東京医科歯科大学, 難治疾患研究所, 准教授 (00517518)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2011: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | WNK / PHAII / ショウジョウバエ / Lhx8/Awh / 細胞内シグナル / 神経分化 / 標的遺伝子 / Lhx8 / WNK1 / WNK4 / 高血圧症 / Fray / Arroehead / シグナル伝達 / OSR1 |
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| Research Abstract |
WNK kinase family is conserved among many species and regulates SPAK/OSR1 and ion co-transporters. Some mutations in human WNK1 or WNK4 are associated with Pseudohypoaldosteronism type II, a form of hypertension. Here, we identify a new target gene in WNK signaling, Arrowhead and Lhx8, which is a mammalian homologue of Drosophila Arrowhead. In Drosophila, WNK was shown to genetically interact with Arrowhead. In Wnk1 knockout mice, levels of Lhx8 expression were reduced. Ectopic expression of WNK1, WNK4 or Osr1 in mammalian cells induced the expression of the Lhx8. Moreover, neural specification was inhibited by the knockdown of both Wnk1 and Wnk4 or Lhx8. Drosophila WNK mutant caused defects in axon guidance during embryogenesis. These results suggest that WNK signaling is involved in the morphological and neural development via Lhx8/Arrowhead.
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