2023 Fiscal Year Final Research Report
Elucidation of gene network organized by CtBP1/2 in mouse limb development
| Project/Area Number |
21K09784
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56070:Plastic and reconstructive surgery-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | エピジェネティクス / 四肢形成 / 合指症 / ポリコム複合体 / CtBP1/2 |
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| Outline of Final Research Achievements |
Deletion of a known co-repressor, Ctbp1/2, in a limb bud-specific manner resulted in a phenotype that was very similar to that of syndactyly, however, it remained unclear which gene network failure could be responsible. By performing the single cell multiome analysis, we found that Aldh1a2 expression was significantly reduced in Ctbp1/2-dKO limb bud, suggesting that Retinoic acid signaling, which regulates the interdigital cell death, was insufficient under the lack of CtBP1/2. We went onto assess whether administration of Retinoic acid to the fetus via mother could rescue the syndactyly phenotype and found a partial alleviation of digital fusion at distal tip. We also revealed that CtBP1/2 works as a potential co-factor of HOX13 and HOX13-dependent activation of Aldh1a2 requires CtBP1/2. In this research, we newly propose that CtBP1/2 and HOX13 potentially interact to facilitate the appropriate autopod patterning.
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| Free Research Field |
発生生物学
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| Academic Significance and Societal Importance of the Research Achievements |
合指症は生まれつき隣り合った指が癒合した状態であり、外科手術による治療が一般的である。Hoxd13の変異が発症原因として知られているタイプもあるが、多くのタイプでは原因がよくわかっていないのが現状である。本研究成果から、Aldh1a2遺伝子の発現低下に起因する指間細胞死の誘導不全が合指症の原因の一つとなりうることが示された。これにより、胎仔期のレチノイン酸投与による療法だけでなく、局所的に細胞死を誘導することができれば、新しい治療法の開発に繋がると期待できる。
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