Homeobox code-mediated regulatory mechanisms of mammalian heterodonty

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06651
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Tohoku University
• Principal Investigator: Wakamatsu Yoshio 東北大学, 医学系研究科, 准教授 (60311560)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 異形歯性 / 歯 / 発生 / 進化 / 哺乳類 / Msx1 / エンハンサー / 次世代シークエンス

Outline of Final Research Achievements

In this study, I examined the regulation of Msx1 gene in the jaw primordium, as Msx1 is important for the establishment of mammalian heterodonty. I identified genomic sequences interacting with the Msx1 promoter region in chicken jaw primordium by 4C-seq analysis. Among such sequences, the ones highly conserved among vertebrate species were isolated, and GFP reporter genes were constructed. The enhancer activities of those reporters were tested in chicken embryos, and I have identified front-nasal, maxillary, and mandibular enhancers, suggesting that the Msx1 expression in the jaw primordium is established by a combination of distinct enhancer elements. I also performed similar analyses with mouse tissues, and found some mammal-specific and placental mammal-specific enhancers. These results indicate that, during mammalian evolution, the regulatory mechanisms of Msx1 expression have been modified to achieve the heterodonty.

Free Research Field

発生学

Academic Significance and Societal Importance of the Research Achievements

異形歯性の制御機構を明らかにすることは哺乳類の進化を理解するために重要であるが、本研究により哺乳類の進化過程でおきたMsx1遺伝子の発現制御の変化を捉えることができたのは大きな前進である。また、4C-seqという次世代シークエンス技術を用いた最新の解析手法を導入してより網羅的にMsx1遺伝子の組織特異的エンハンサー候補配列を抽出することに成功し、これまでの手法より効率的なエンハンサーの同定につながったことは、遺伝子発現制御の研究分野において大きく貢献したと考えられる。
Msx1遺伝子の異常はヒトの部分性無歯症の原因であり、本研究は医学的観点からも重要な情報を提供したと言えるだろう。