Identification of transcription networks associated with oral clefts

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K11004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: FUNATO Noriko 東京医科歯科大学, 統合研究機構, 准教授 (10376767)
• Research Collaborator: YANAGISAWA Hiromi ; RICHARDSON James ; SRIVASTAVA Deepak ; NAKAMURA Masataka ; SAGA Yumiko ; KOKUBO Hiroki
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 口蓋裂 / 下顎 / Hand2 / Tbx1 / 転写因子 / 脊椎動物

Outline of Final Research Achievements

Oral clefts, the most frequent congenital birth defects in humans, are multifactorial disorders caused by genetic and environmental factors. Although genes related to genetic disorders associated with oral cleft phenotypes are known, a gap between detecting these associations and interpretation of their biological importance has remained. We grouped the candidate genes on the basis of different functional categories to gain insight into the genetic etiology of oral clefts.
In addition, we provided evidence that transcription factor TBX1 maintains normal growth and development of palatal shelves, mediated through the regulation of genes involved in muscle cell differentiation, nervous system development, and biomineral tissue development. We also reported that transcription factor HAND2 is sufficient for upper jaw (maxilla)-to-mandible transformation by regulating the expression of homeobox transcription factors in mice.

Free Research Field

形態系基礎歯科学

Academic Significance and Societal Importance of the Research Achievements

T-box 型転写因子をコードするTBX1は、新生児4000人に1人に認められる22q11.2欠失症候群 (DiGeorge症候群、velo-cardio-facial症候群) の疾患遺伝子候補の一つである (OMIM #188400)。本研究により、22q11.2欠失症候群と他の症候群とが口蓋裂の発生において関わりがあることが明らかになった。一方、口蓋および下顎の獲得は脊椎動物の進化において最も重要なステップであるが、bHLH型転写因子Hand2の遺伝子改変マウスを用いた解析により、遺伝子レベルで顎の進化の一端を解明した。これらは、動物形態進化学的にも意義があるといえる。