Characterization of neural crest cells migrating into the heart

• Project/Area Number: 26670396
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokyo
• Principal Investigator: KURIHARA Hiroki 東京大学, 大学院医学系研究科, 教授 (20221947)
• Co-Investigator(Renkei-kenkyūsha): WADA Youichiro 東京大学, アイソトープ総合センター, 教授 (10322033) ; TOMITA Sachiko ヤマザキ学園大学, 動物看護学部, 教授 (40231451) ; KURIHARA Yukiko 東京大学, 大学院医学系研究科, 講師 (80345040)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 循環器 / 分子心臓学 / 発生・分化 / 幹細胞

Outline of Final Research Achievements

In this study, we investigated the origin and fate of neural crest cells migrating into the heart through experiments using mouse and avian embryos. We found that cells originating from the preotic region of the neural crest, as well as “cardiac neural crest cells” derived from the more caudal post-otic region, migrate into the heart and differentiate into various cell types including coronary artery smooth muscle cells and mesenchymal cells in the semiluminal valves and myocardial walls. Single-cell analysis of gene expression patterns revealed the existence of a subset of neural crest cells expressing some stem cell markers (e.g. c-Kit), indicating the maintenance of the stemness with multipotency in a neural crest population within the heart.

Research Products

• [Journal Article] Developmental mechanisms of the tympanic membrane in mammals and non-mammalian amniotes (2016)
  • Author(s): Takechi, M., Kitazawa, T., Hirasawa, T., Hirai, T., Iseki, S., Kurihara, H., Kuratani, S.
  • Journal Title: Congenital Anomalies Volume: 56 Issue: 1 Pages: 12-17
  • DOI: 10.1111/cga.12132
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Facial whisker pattern is not sufficient to instruct a whisker-related topographic map in the mouse somatosensory brainstem. (2015)
  • Author(s): Laumonnerie C, Bechara A, Vilain N, Kurihara Y, Kurihara H,Rijli FM.
  • Journal Title: Development. Volume: 142(21) Pages: 3704-3712
  • DOI: 10.1242/dev.128736
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids. (2015)
  • Author(s): Kitazawa T, Takechi M, Hirasawa T, Adachi N, Narboux-Neme N, Kume H, Maeda K, Hirai T, Miyagawa-Tomita S, Kurihara Y, Hitomi J, Levi G, Kuratani S, Kurihara H
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 6853-6853
  • DOI: 10.1038/ncomms7853
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Distinct effects of Hoxa2 overexpression in cranial neural crest populations reveal that the mammalian hyomandibular-ceratohyal boundary maps within the styloid process. (2015)
  • Author(s): Kitazawa T, Fujisawa K, Narboux-Neme N, Arima Y, Kawamura Y, Inoue T, Wada Y, Kohro T, Aburatani H, Kodama T, Kim KS, Sato T, Uchijima Y, Maeda K, Miyagawa-Tomita S, Minoux M, Rijli FM, Levi G, Kurihara Y, Kurihara H
  • Journal Title: Developmental Biology Volume: 15 Issue: 2 Pages: 162-174
  • DOI: 10.1016/j.ydbio.2015.04.007
  • Peer Reviewed / Open Access
• [Journal Article] Mutations in the endothelin receptor type A cause mandibulofacial dysostosis with alopecia. (2015)
  • Author(s): Gordon CT, Weaver KN, Zechi-Ceide RM, Madsen EC, Tavares AL, Oufadem M, Kurihara Y, （18名）, Kurihara H, .et al.
  • Journal Title: Am J Hum Genet. Volume: 96(4) Issue: 4 Pages: 519-531
  • DOI: 10.1016/j.ajhg.2015.01.015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Simple model of pH-induced protein denaturation. (2015)
  • Author(s): Hidaka T, Shimada A, Nakata Y, Kodama H, Kurihara H, Tokihiro T, Ihara S.
  • Journal Title: Phys Rev E Stat Nonlin Soft Matter Phys. Volume: 92(1-1) Pages: 012709-012709
  • Peer Reviewed
• [Journal Article] Autonomy and non-autonomy of angiogenic cell movements revealed by experiment-driven mathematical modeling (2015)
  • Author(s): Sugihara K, Nishiyama K, Fukuhara S, Uemura A, Arima S, Kobayashi R, Kohn-Luque A, Mochizuki N, Suda T, Ogawa S, Kurihara H
  • Journal Title: Cell Rep Volume: 13 Issue: 9 Pages: 1814-1827
  • DOI: 10.1016/j.celrep.2015.10.051
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dysregulated YAP1/TAZ and TGF signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice (2015)
  • Author(s): Nishio, M., Sugimachi, K., Goto, H., Wang, J., Morikawa, T., Miyachi, Y., Takano, Y., Hikasa, H., Itoh, T., Suzuki, S.O., Kurihara, H., Aishima, S., Leask, A., Sasaki, T., Nakano, T., Nishina, H., Nishikawa, Y., Sekido, Y., Nakao, K., Shin-ya, K., Mimori, K. and Suzuki, A.
  • Journal Title: PNAS Volume: 113 Issue: 1 Pages: 71-80
  • DOI: 10.1073/pnas.1517188113
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Postotic and preotic neural crest cells differently contribute to thyroid development. (2015)
  • Author(s): Kazuhiro Maeda, Rieko Asai, Kazuaki Maruyama, Yukiko Kurihara, Toshio Nakanishi, Hiroki Kurihara, Sachiko Miyagawa-Tomita.
  • Journal Title: Dev Biol Volume: 409 Issue: 1 Pages: 72-83
  • DOI: 10.1016/j.ydbio.2015.10.026
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids. (2015)
  • Author(s): Kitazawa T, Takechi M, Hirasawa T, Adachi N, Narboux-Nême N, Kume H, Maeda K, Hirai T, Miyagawa-Tomita S, Kurihara Y, Hitomi J, Levi G, Kuratani S, Kurihara H.
  • Journal Title: Nat. Commun. Volume: 14 Pages: 18224-18224
  • Peer Reviewed / Open Access
• [Journal Article] Lysocin e is a new antibiotic that targets menaquinone in the bacterial membrane (2015)
  • Author(s): Hamamoto H, Urai M, Ishii K, Yasukawa J, Paudel A, Murai M, Kaji T, Kuranaga T, Hamase K, Katsu T, Su J, Adachi T, Uchida R, Tomoda H, Yamada M, Souma M, Kurihara H, Inoue M, Sekimizu K.
  • Journal Title: Nature Chemical Biology Volume: 11 Issue: 2 Pages: 127
  • DOI: 10.1038/nchembio.1710
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart (2014)
  • Author(s): Arita Y, Nakaoka Y, Matsunaga T, Kidoya H, Yamamizu K, Arima Y, Kataoka-Hashimoto T, Ikeoka K, Yasui T, Masaki T, Yamamoto K, Higuchi K, Park JS, Shirai M, Nishiyama K, Yamagishi H, Otsu K, Kurihara H, Minami T, Yamauchi-Takihara K, Koh GY, Mochizuki N, Takakura N, Sakata Y, Yamashita JK, Komuro I
  • Journal Title: Nat Commun Volume: 5 Issue: 1 Pages: 4452-4452
  • DOI: 10.1038/ncomms5552
  • Peer Reviewed / Open Access
• [Journal Article] SIRT3 positively regulates the expression of folliculogenesis- and luteinization-related genes and progesterone secretion by manipulating oxidative stress in human luteinized granulosa cells (2014)
  • Author(s): Fu H, Wada-Hiraike O, Hirano M, Kawamura Y, Sakurabashi A, Shirane A, Morita Y, Isono W, Oishi H, Koga K, Oda K, Kawana K, Yano T, Kurihara H, Osuga Y, Fujii T.
  • Journal Title: Endocrinology Volume: 155 Issue: 8 Pages: 3079
  • DOI: 10.1210/en.2014-1025
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 血管新生における細胞動態の実験及び数理解析 (2016)
  • Author(s): 栗原裕基
  • Organizer: 生命動態システム科学四拠点・CREST・PRESTO・QBiC 合同シンポジウム「生命動態の分子メカニズムと数理」
  • Place of Presentation: 広島県広島市
  • Year and Date: 2016-03-26
  • Invited
• [Presentation] Semaphorin3E-PlexinD1 シグナルは冠動脈形成に重要な役割を果たす (2016)
  • Author(s): 丸山和晃，富田－宮川幸子，有馬勇一郎，浅井理恵子，植村明嘉, 瀬谷大貴，吉田豊, Man Fanny, 栗原由紀子，栗原裕基
  • Organizer: 血管生物医学会 若手研究会
  • Place of Presentation: 宮崎県仙台市
  • Year and Date: 2016-03-04
• [Presentation] 心溜出路に遊走する神経堤細胞の系譜とレチノイン酸の作用の検討 (2015)
  • Author(s): 瀬谷大貴、富田－宮川幸子、有馬勇一郎、淺井理恵子、丸山和晃、内島泰信、栗原由紀子、栗原裕基
  • Organizer: 第14回日本心臓血管発生研究会
  • Place of Presentation: 福島県郡山市
  • Year and Date: 2015-12-19
• [Presentation] Semaphorin3E-PlexinD1シグナルは冠血管発生に重要である (2015)
  • Author(s): 丸山和晃，富田－宮川幸子，有馬勇一郎，浅井理恵子，植村明嘉, 瀬谷大貴，吉田豊, Man Fanny, 栗原由紀子，栗原裕基
  • Organizer: 第14回日本心臓血管発生研究会
  • Place of Presentation: 福島県郡山市
  • Year and Date: 2015-12-19
• [Presentation] 単一細胞トラッキングを用いた血管内皮細胞動態解析 (2015)
  • Author(s): 田久保直子，苗村和明，吉田亮，徳永旭将，広瀬修，内島泰信，栗原由紀子，栗原裕基
  • Organizer: 第23回日本血管生物医学会学術集会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-12
• [Presentation] マウス脳底動脈拡張症モデルの作成・解析 (2015)
  • Author(s): 苗村和明、中冨浩文、田口明糸、和田洋一郎、斉藤延人、栗原裕基苗村和明、中冨浩文、田口明糸、和田洋一郎、斉藤延人、栗原裕基
  • Organizer: 第23回日本血管生物医学回学術集会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-11
• [Presentation] Semaphorin3E-PlexinD1 シグナルは冠動脈形成に重要な役割を果たす (2015)
  • Author(s): 丸山和晃，富田－宮川幸子，有馬勇一郎，浅井理恵子，植村明嘉, 瀬谷大貴，吉田豊, Man Fanny, 栗原由紀子，栗原裕基
  • Organizer: 第23回日本血管生物医学会学術集会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-11
• [Presentation] in vitro 血管新生のタイムラプスイメージングと細胞トラッキング (2015)
  • Author(s): 田久保直子
  • Organizer: 生命ダイナミクスの数理とその応用：理論からのさらなる深化（数学協働プログラム）
  • Place of Presentation: 東京都文京区
  • Year and Date: 2015-12-10
• [Presentation] 形態形成における long noncodingRNA: Evf2の機能解析 (2015)
  • Author(s): 栗原由紀子
  • Organizer: 第38回日本分子生物学会年会（BMB2015)
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-02
• [Presentation] A homeotic transformation in neural crest-specific Dlx5-overexpressing mice.神経堤細胞特異的Dlx5過剰発現マウスにおける顎顔面のトランスフォーメーション (2015)
  • Author(s): Miki Shimizu, Taro Kitazawa, Yumiko Kawamura, Nicolas Narboux-Nême, Giovanni Levi, Youichiro Wada, Yasunobu Uchijima, Yukiko Kurihara, Hiroki Kurihara
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-02
• [Presentation] Semaphorin3E-PlexinD1 signaling is important for coronary artery formation (2015)
  • Author(s): 丸山和晃，富田－宮川幸子，有馬勇一郎，浅井理恵子，植村明嘉, 瀬谷大貴，吉田豊, Man Fanny, 栗原由紀子，栗原裕基
  • Organizer: 第38回日本分子生物学会年会（BMB2015)
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-01
• [Presentation] からだのかたちづくりを科学する (2015)
  • Author(s): 栗原裕基
  • Organizer: 生命のダイナミクスと数学 公開講座
  • Place of Presentation: 東京都文京区
  • Year and Date: 2015-11-21
  • Invited
• [Presentation] マウス脳底動脈露出手技の確立及びマウス脳底動脈拡張症モデルの作成・解析 (2015)
  • Author(s): 苗村和明、中冨浩文、宮脇哲、越智崇、伊藤明博、今井英明、栗原裕基、斉藤延人
  • Organizer: 第74回日本脳神経外科学会学術総会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2015-10-15
• [Presentation] 血管新生における内皮細胞動態ライブイメージング (2015)
  • Author(s): 田久保直子，苗村和明，吉田亮，徳永旭将，広瀬修，内島泰信，栗原由紀子，栗原裕基
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2015-09-14
• [Presentation] A homeotic transformation in Dlx5-overexpressing mice give a hint to form a dorsoventral axis. (2015)
  • Author(s): Miki Shimizu, Taro Kitazawa, Yumiko Kawamura, Nicolas Narboux-Nême, Giovanni Levi, Youichiro Wada, Yasunobu Uchijima, Yukiko Kurihara, Hiroki Kurihara
  • Organizer: 第15回東京大学生命科学シンポジウム
  • Place of Presentation: 東京都文京区
  • Year and Date: 2015-06-27
• [Presentation] Dlx5-overexpression mice show a homeotic transformation in the upper jaw into lower jaw-like structures.Dlx5過剰発現マウスにおける上顎の下顎構造へのトランスフォーメーション (2015)
  • Author(s): Miki Shimizu, Taro Kitazawa, Yumiko Kawamura, Nicolas Narboux-Nême, Giovanni Levi, Yasunobu Uchijima, Yukiko Kurihara, Hiroki Kurihara
  • Organizer: 第48回日本発生生物学会
  • Place of Presentation: 茨城県つくば市
  • Year and Date: 2015-06-03
• [Presentation] Semaphorin3E-PlexinD1 signaling is important for coronary artery formation (2015)
  • Author(s): 丸山和晃，富田－宮川幸子，有馬勇一郎，浅井理恵子，植村明嘉, 瀬谷大貴，吉田豊, Man Fanny, 栗原由紀子，栗原裕基
  • Organizer: 第48回日本発生生物学会
  • Place of Presentation: 茨城県つくば市
  • Year and Date: 2015-06-03
• [Presentation] Independent origins of the tympanic membrane and middle ear in different amniote taxa. (2015)
  • Author(s): Taro Kitazawa, Masaki Takechi, Tatsuya Hirasawa, Nicolas Narboux-Neme, Hideaki Kume, Kazuhiro Maeda, Sachiko Miyagawa-Tomita, Yukiko Kurihara, Giovanni Levi, Shigeru Kuratani, Hiroki Kurihara.
  • Organizer: 第47回日本発生生物学会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2015-05-27 – 2015-05-30
• [Presentation] Semaphorin3E-PlexinD1 signalimg is importamt for coronary artery formation (2015)
  • Author(s): Kazuaki Maruyama, Sachiko Miyagawa-Tomita, Yuichiro Arima, Daiki Seya, Rieko Asai, Akiyoshi Uemura, Yutaka Yoshida, Mann Fanny, Yukiko Kurihara, Hiroki Kurihara
  • Organizer: Weinstein 2015
  • Place of Presentation: USA ,Boston
  • Year and Date: 2015-04-30
  • Int'l Joint Research
• [Presentation] 単一細胞ライブイメージングを用いた内皮細胞動態解析 (2015)
  • Author(s): 田久保直子，内島泰信，金井政宏，苗村和明，栗原由紀子，栗原裕基.
  • Organizer: 生命動態システム科学四拠点・CREST・PREST合同シンポジウム
  • Place of Presentation: 京都府京都市
  • Year and Date: 2015-03-16 – 2015-03-17
• [Presentation] The role of Semaphorin3E-PlexinD1 signaling in heart morphogenesis. (2014)
  • Author(s): Kazuaki Maruyama , Sachiko Miyagawa-Tomita , Yuichiro Arima , Daiki Seya , Rieko Asai , Akiyoshi Uemura , Yutaka Yoshida , Mann Fanny , Yukiko Kurihara , Hiroki Kurihara.
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Preotic neural crest cells contribute to thyroid bilobation. (2014)
  • Author(s): Kazuhiro Maeda, Rieko Asai, Hiroki Kurihara, Sachiko Miyagawa-Tomita.
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Dlx5-overexpression mice show a homeotic transformation in the upper jaw into lower jaw-like structures. (2014)
  • Author(s): Miki Shimizu, Taro Kitazawa, Yumiko Kawamura, Nicolas Narboux-Nême, Giovanni Levi, Yasunobu Uchijima, Yukiko Kurihara, Hiroki Kurihara
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] エンドセリン-Dlx5/6遺伝子変異マウスにおけるIRDS様肺病変 (2014)
  • Author(s): 栗原由紀子、淺井理恵子、河村悠美子、栗栖健、栗原裕基
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 単一細胞ライブイメージングを用いた血管新生の細胞動態解析 (2014)
  • Author(s): 田久保 直子，苗村 和明，内島 泰信，栗原 由紀子，栗原 裕基.
  • Organizer: 「生命動態の理解と制御のための基盤技術の創出」研究領域 第3回領域会議
  • Place of Presentation: 沖縄県国頭郡
  • Year and Date: 2014-10-28 – 2014-10-29
• [Presentation] 胚外壁側葉中胚葉は心血管形成に寄与する (2014)
  • Author(s): Rieko Asai, Sachiko Miyagawa-Tomita, Yukiko Kurihara , Hiroki Kurihara.
  • Organizer: 第13回心臓血管発生研究会
  • Place of Presentation: 福島県郡山市
  • Year and Date: 2014-10-17 – 2014-10-18
• [Presentation] Semaphorin3E, PlexinD1の心臓血管系発生における役割の解明 (2014)
  • Author(s): Kazuaki Maruyama , Sachiko Miyagawa-Tomita , Yuichiro Arima , Daiki Seya , Rieko Asai , Akiyoshi Uemura , Yutaka Yoshida , Mann Fanny , Yukiko Kurihara , Hiroki Kurihara.
  • Organizer: 第13回心臓血管発生研究会
  • Place of Presentation: 福島県郡山市
  • Year and Date: 2014-10-17 – 2014-10-18
• [Presentation] Homeotic transformation of the upper jaw into lower jaw-like structures in Dlx5-overexpressing mice. (2014)
  • Author(s): Miki Shimizu, Taro Kitazawa, Yumiko Kawamura, Nicolas Narboux-Nême, Giovanni Levi, Yasunobu Uchijima, Yukiko Kurihara, Hiroki Kurihara.
  • Organizer: 第47回日本発生生物学会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2014-05-27 – 2014-05-30
• [Remarks] 東京大学大学院医学系研究科 代謝生理化学教室
  • URL: http://bio.m.u-tokyo.ac.jp/home-j.html