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Genetic and enviromental interaction for the etiology of craniofacial defect

Research Project

Project/Area Number 16K15836
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Orthodontics/Pediatric dentistry
Research InstitutionOsaka University

Principal Investigator

Kurosaka Hiroshi  大阪大学, 歯学部附属病院, 講師 (20509369)

Research Collaborator NAKAYA AKIHIRO  
KIKUCHI MASATAKA  
MASHIMO TOMOJI  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords顎顔面形成不全 / ゲノム / 稀少疾患 / 多因子性疾患 / レチノイン酸シグナル / 口唇口蓋裂 / エタノール / 遺伝的要因 / 環境的要因 / アルコール / 顎顔面発生 / 遺伝 / 環境因子
Outline of Final Research Achievements

Craniofacial development is a complex process that involves sequential growth and fusion of the facial prominences. When these processes fail, congenital craniofacial anomalies can occur. Cleft palate (CP) is one of the most common congenital craniofacial anomalies in humans and can be caused by either single or multiple genetic and environmental factor(s). In this research project we have performed multiple exome sequencing in familial craniofacial disorders. From this analysis, we discovered novel single nucleotide mutation which causes amino acid transition in DLC1 (Deleted in Liver Cancer 1) in two independent families. We have also identified novel gene mutation which is related to PTH signaling pathway in familial craniosynostosis.

Academic Significance and Societal Importance of the Research Achievements

胎生期における顎顔面の形成は複雑かつ精巧に行われ、その発生過程の不具合は口唇口蓋裂等の顎顔面形成不全の原因となる。同疾患は多因子性疾患であり、胎生期における遺伝的要因と環境的要因に大きな影響を受けて発病する事が知られている。本研究では顎顔面形成不全に関わる新規遺伝子変異を多数同定した。この事は将来的な同疾患の新規診断法報や治療方法の確立に大きく寄与する。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (36 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (23 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Int'l Joint Research] Stowers Institute for Medical Research(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Stowers Institute for Medical Research/University of Lousville(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Stowers Institute for Medical Research/University of Louisville(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Stage- and tissue-specific effect of cyclophosphamide during tooth development2019

    • Author(s)
      Nakatsugawa Kohei、Kurosaka Hiroshi、Inubushi Toshihiro、Aoyama Gozo、Isogai Yukako、Usami Yu、Toyosawa Satoru、Yamashiro Takashi
    • Journal Title

      European Journal of Orthodontics

      Volume: - Issue: 5 Pages: 519-530

    • DOI

      10.1093/ejo/cjz002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel PTCH1 mutation in basal cell nevus syndrome with rare craniofacial features2019

    • Author(s)
      Murata Y, Kurosaka H, Ohata Y, Aikawa T, Takahata S, Fujii K, Miyashita T, Morita C, Inubushi T, Kubota T, Sakai N, Ozono K, Kogo M, Yamashiro T.
    • Journal Title

      Human Genome Variation

      Volume: 6 Issue: 1 Pages: 16-16

    • DOI

      10.1038/s41439-019-0047-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Orthodontic-Surgical Approach for Treating Skeletal Class III Malocclusion With Severe Maxillary Deficiency in Isolated Cleft Palate2018

    • Author(s)
      Nakatsugawa Kohei、Kurosaka Hiroshi、Mihara Kiyomi、Tanaka Susumu、Aikawa Tomonao、Kogo Mikihiko、Yamashiro Takashi
    • Journal Title

      The Cleft Palate-Craniofacial Journal

      Volume: 56 Issue: 3 Pages: 400-407

    • DOI

      10.1177/1055665618777573

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Runx1-Stat3-Tgfb3 signaling network regulating the anterior palatal development2018

    • Author(s)
      Sarper Safiye E.、Kurosaka Hiroshi、Inubushi Toshihiro、Ono Minagi Hitomi、Kuremoto Koh-ichi、Sakai Takayoshi、Taniuchi Ichiro、Yamashiro Takashi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 29681-3

    • DOI

      10.1038/s41598-018-29681-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors2018

    • Author(s)
      Sarper Safiye E.、Inubushi Toshihiro、Kurosaka Hiroshi、Ono Minagi Hitomi、Kuremoto Koh-ichi、Sakai Takayoshi、Taniuchi Ichiro、Yamashiro Takashi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 29317-6

    • DOI

      10.1038/s41598-018-29317-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Choanal atresia and stenosis: Development and diseases of the nasal cavity2018

    • Author(s)
      Kurosaka Hiroshi
    • Journal Title

      Wiley Interdisciplinary Reviews: Developmental Biology

      Volume: 8 Issue: 1

    • DOI

      10.1002/wdev.336

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ventral neural patterning in the absence of a Shh activity gradient from the floorplate2018

    • Author(s)
      Iulianella Angelo, Daisuke Sakai, Hiroshi Kurosaka, Paul Trainor
    • Journal Title

      Developmental Dynamics

      Volume: 247 Issue: 1 Pages: 170-184

    • DOI

      10.1002/dvdy.24590

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Runx1 mediates the development of the granular convoluted tubules in the submandibular glands2017

    • Author(s)
      Ono Minagi Hitomi、Sarper Safiye Esra、Kurosaka Hiroshi、Kuremoto Koh-ichi、Taniuchi Ichiro、Sakai Takayoshi、Yamashiro Takashi
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 9 Pages: 0184395-0184395

    • DOI

      10.1371/journal.pone.0184395

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia.2017

    • Author(s)
      Kurosaka H, Wang Q, Sandell L, Yamashiro T, Trainor PA.
    • Journal Title

      Human Molecular Genetics

      Volume: 26 Issue: 7 Pages: 1268-1279

    • DOI

      10.1093/hmg/ddx031

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A quantitative method for defining high-arched palate using the Tcof1+/- mutant mouse as a model.2016

    • Author(s)
      Conley ZR, Hague M, Kurosaka H, Dixon J, Dixon MJ, Trainor PA.
    • Journal Title

      Developmental biology

      Volume: 15 Issue: 2 Pages: 296-305

    • DOI

      10.1016/j.ydbio.2015.12.020

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 口唇口蓋裂の新規原因遺伝子DLC1の機能解析2018

    • Author(s)
      黒坂 寛、森田 知里、山城隆
    • Organizer
      第42回 日本口蓋裂学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] シクロホスファミド投与が多様な歯牙形成不全を誘発する2018

    • Author(s)
      中津川 昂平、黒坂 寛、山城 隆
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] シクロホスファミド投与がマウスの大臼歯の歯胚形成に与える影響2018

    • Author(s)
      中津川 昂平、黒坂 寛、犬伏 俊博、山城 隆
    • Organizer
      第77回 日本矯正歯科学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Investigating the role of retinoic acid signaling during upper face development2018

    • Author(s)
      Yanran Wu, Hiroshi Kurosaka, Qi Wang, Paul Trainor and Takashi Yamashiro
    • Organizer
      第77回日本矯正歯科学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 著しい骨格性下顎前突および開咬を呈し,Opitz症候群の疑いのある両側性唇顎口蓋裂の一症例2018

    • Author(s)
      岡 綾香、黒坂 寛、中津川 昂平、三原 聖美、田中 晋、古郷 幹彦、山城 隆
    • Organizer
      第77回 日本矯正歯科学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 歯根吸収に配慮して全顎的矯正治療を行ったTurner症候群患者の一治療例2018

    • Author(s)
      磯貝 由佳子, 岡 綾香、中津川 昂平、黒坂 寛、山城 隆
    • Organizer
      第77回 日本矯正歯科学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 下顎前突治療における外科と矯正のチームアプローチ:大阪大学歯学部附属病院での実際2018

    • Author(s)
      山城 隆、黒坂 寛、伊藤 慎将、相川 友直
    • Organizer
      日本顎変形症学会第14回教育研修会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨細胞への分化誘導法を確立する新たなアプローチ2018

    • Author(s)
      村田有香、犬伏俊博、山本沙優里、森田知里、伊藤慎将、黒坂 寛、山城 隆
    • Organizer
      第77回日本矯正歯科学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cbfb is involved in the anteriorly Specific Palatogenesis2017

    • Author(s)
      Sarper S, Kurosaka H, Mihara K, Ono H, Yamashiro T
    • Organizer
      97th General Session & Exhibition of the International Association for Dental Research
    • Related Report
      2017 Research-status Report
  • [Presentation] Retinoic-acid-induced defective branchiomeric muscle by downregulation of Pitx22017

    • Author(s)
      Wang Q, Yamashiro T, Kurosaka H
    • Organizer
      Japanese Association for Dental Research
    • Related Report
      2017 Research-status Report
  • [Presentation] The role of retinoid signaling for maxillary development2017

    • Author(s)
      Kurosaka H
    • Organizer
      Oral and Craniofacial Development and Disease 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Runx/Cbfb signaling regulating Stat3 during enamel formation2017

    • Author(s)
      Sarper SE, Kurosaka H, Ono Minagi H, Sakai T, Yamashiro T
    • Organizer
      Oral and Craniofacial Development and Disease 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Runx1-Stat3-Tgfb3 signaling network regulating the anterior palatal development2017

    • Author(s)
      Sarper SE, Kurosaka H, Ono Minagi H, Sakai T, Yamashiro T
    • Organizer
      Oral and Craniofacial Development and Disease 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Effect of Cyclophosphamide on the developing teeth of neonatal mouse2017

    • Author(s)
      Nakatsugawa K, Kurosaka H, Yamashiro T
    • Organizer
      Oral and Craniofacial Development and Disease 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] The role of retinoic acid signaling in upper incisor development2017

    • Author(s)
      Wu Y, Wang Q, Sandell L, Kikuchi M, Nakaya A, Trainor P, Kurosaka H, Yamashiro T
    • Organizer
      Oral and Craniofacial Development and Disease 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Retinoic-acid-induced defective branchiomeric muscle by downregulation of Pitx22017

    • Author(s)
      Qi Wang, Takashi Yamashiro, Hiroshi Kurosaka
    • Organizer
      Gordon Research Conference Craniofacial Morphogenesis and Tissue Regeneration
    • Related Report
      2017 Research-status Report
  • [Presentation] Novel mutation of DLC1 in familial cleft palate case2017

    • Author(s)
      Yanran Wu, Qi Wang, Chisato Morita, Akihiro Nakaya, Atsuko Okazaki, Kaori Kobayashi, Masataka Kikuchi, Tomoji Mashimo, Yoshihiro Uno, Shinya Oki, Takashi Yamashiro
    • Organizer
      Gordon Research Conference Craniofacial Morphogenesis and Tissue Regeneration
    • Related Report
      2017 Research-status Report
  • [Presentation] Rdh10 の時期特異的な機能阻害は口唇口蓋裂や後鼻孔閉鎖の原因となる2017

    • Author(s)
      黒坂 寛
    • Organizer
      第41回日本口蓋裂学会総会・学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] レチノイン酸シグナルとShh シグナルの相互作用が口蓋裂及ぼす役割2017

    • Author(s)
      Wang Qi、山城 隆、黒坂 寛
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Analyzing the variation of orthodontic treatment in patients with cleft lip and/or palate.2016

    • Author(s)
      Hiroshi Kurosaka, Chihiro Tanikawa, Kayo Nishimura, Shinsuke Ito and Takashi Yamashiro.
    • Organizer
      The 11th Congress of the Asian Pacific Craniofacial Association.
    • Place of Presentation
      京都国際会議場(京都府、京都市)
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] レチノイン酸シグナルとShhシグナルの相互作用が顔面形成に及ぼす役割2016

    • Author(s)
      Wang Qi、山城 隆、黒坂 寛
    • Organizer
      58回 歯科基礎医学会学術大会
    • Place of Presentation
      札幌コンベンションセンター(北海道、札幌市)
    • Year and Date
      2016-08-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 口蓋発生及び後鼻孔形成におけるレチノイン酸シグナリングの生物学的役割2016

    • Author(s)
      黒坂 寛、Wang Qi、山城 隆
    • Organizer
      第40回 日本口蓋裂学会総会・学術集会
    • Place of Presentation
      ナレッジキャピタル(大阪府、大阪市)
    • Year and Date
      2016-05-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Critical roles of Rdh10 in craniofacial development2016

    • Author(s)
      Hiroshi Kurosaka, Qi Wang, Lisa Sandell, Masataka Kikuchi, Akihiro Nakaya and Paul Trainor.
    • Organizer
      The 13th International Congress of Human Genetics.
    • Place of Presentation
      奈良100年会館(奈良県、奈良市)
    • Year and Date
      2016-04-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2022-02-21  

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