| Project/Area Number |
23K14201
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 44020:Developmental biology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Trush Olena 国立研究開発法人理化学研究所, 生命機能科学研究センター, 基礎科学特別研究員 (20869143)
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| Project Period (FY) |
2023-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2024: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | kidney / nephron / S-shaped body / development / organoid |
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| Outline of Research at the Start |
As an outline, I hope to reveal the regulatory mechanism for nephron morphogenesis at S-shaped body stage. This finding will get immediate application in the generation of improved kidney organoids to achieve better morphology of nephrons in vitro and reduce heterogeneity of kidney organoids.
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| Outline of Annual Research Achievements |
In this project we revealed that Wnt4 ligand is crucial for the formation S-shaped body(SSB)- an important morphological feature of early nephron.
We also found that the induction of nephrogenesis by artificial Wnt activator (CHIR99021) causes abnormal branching of the nephron on the edge of distal and proximal region, and, as a result, formation of T-shaped bodies instead of SSB. The branching areas were characterized by the expanded expression of Jag1 ligand and extensive expansion of the distal part of the nephron, and formation of multiple proximal tubeless withing single nephron. We found that medium supplement with human recombinant Wnt4 ligand or Notch inhibitors could partially rescue the phenotype.
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