Regulation of cell dynamics and differentiation of dental epithelial stem cells during tooth development

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07253
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Jichi Medical University
• Principal Investigator: Takahashi Masanori 自治医科大学, 医学部, 准教授 (20361074)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 歯の形成 / 切歯 / Six1 / Six4 / Masp1 / MASP3

Outline of Final Research Achievements

We examined the functional redundancy of SIX transcription factors in maxillomandibular and incisor formation in mice. Six1/Six4 double-deficient embryos showed hypoplastic maxillomandibular primordia and lacked incisors only in the upper jaw. Six1/Six2/Six4 triple-deficient embryos did not form the upper jaw. We also analyzed downstream genes regulated by Six1/Six4 by RNA sequencing using tissues from the mandibular primordium of Six1/Six4 double-deficient embryos. We found that Alx1 and Masp1 were markedly downregulated in mandibular mesenchymal cells. We also found that Nkx2.5, Lbx1 and Ckmt1 were markedly downregulated in tongue muscle progenitor cells.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

歯は、生活の質を左右する極めて重要な器官である。歯の形成は歯原基のパターン形成に始まり、上皮間葉相互作用を介した複雑な形態形成を経て完成し、一部の上皮細胞は組織幹細胞として維持される。しかしながら、顎および歯の形成における細胞動態や幹細胞の制御機構は未だ不明の点が多い。本研究で明らかにしたSIX1による下顎原基の前後極性制御、SIX1/SIX4による下顎切歯の分化制御と下流制御因子の同定、さらに、SIX1/SIX2/SIX4による上顎形成の新規制御機構は、哺乳類顔面形成の分子細胞機構の理解において学術的に意義があり、顔面形成疾患の発症機序の解明につながると考えられる。