Cell stiffness and extravasation

• Project/Area Number: 15K14358
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: Tohoku University
• Principal Investigator: Saito Daisuke 東北大学, 学際科学フロンティア研究所, 助教 (90403360)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 細胞移動 / 始原生殖細胞 / 胚内動態 / 鳥類 / がん細胞 / 血行性転移 / 血管 / 細胞弾性 / 生殖細胞 / 胚 / ガン

Outline of Final Research Achievements

In avian species, Primordial germ cells (PGCs) use the vascular system to reach somatic gonads. PGCs are flowed by blood circulation and transmigrate from inside of blood vessel to mesenchyme through the wall of blood vessels like metastatic cancer cells. However, there is little understanding of the mechanism underling avian PGC extravasation. I found that PGCs stop circulation at the specific vascular plexus before extravasation. In this plexus, PGCs seemed to stop circulation as they were caught in narrow vascular spaces. raising the possibility that PGCs have high stiffness. Atomic microscopy analysis revealed that PGCs had much higher stiffness than that of other blood cells. I also found that PGC stiffness was mediated by cortical acto-myosin cytoskeleton. Acto-myosin disrupted PGCs did not stop the specific vascular plexus. Thus I conclude that acto-myosin mediated-cell stiffness is critical for avian PGC extravasation.

Research Products

• [Int'l Joint Research] INSERM(フランス)
• [Int'l Joint Research] パスツール研究所/INSERM(フランス)
• [Journal Article] Functional roles of Aves class-specific cis-regulatory elements on macroevolution of bird-specific features (2017)
  • Author(s): Seki, R., Li, C., Fang, Q., Hayashi, S., Egawa, S., Hu, J., Xu, L., Pan, H., Kondo, M., Sato, T., Matsubara, H., Kamiyama, N., Kitajima, K., Saito, D., Liu, Y., Gilbert, M.T.P., Zhou, Q., Xu, X., Shiroishi, T., Irie, N., Tamura, K., and Zhang, G.
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 14229-14229
  • DOI: 10.1038/ncomms14229
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Upstream regulation for initiation of restricted Shh expression in the chick limb bud. (2017)
  • Author(s): Haruka Matusbara
  • Journal Title: Developmental Dynamics Volume: 印刷中 Issue: 5 Pages: 417-430
  • DOI: 10.1002/dvdy.24493
  • Peer Reviewed
• [Journal Article] Early segregation of the adrenal cortex and gonad in chicken embryos (2017)
  • Author(s): Saito Daisuke、Tamura Koji、Takahashi Yoshiko
  • Journal Title: Dev. Growth Differ. Volume: 59 Issue: 7 Pages: 593-602
  • DOI: 10.1111/dgd.12389
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hedgehog-BMP signalling establishes dorsoventral patterning in lateral plate mesoderm to trigger gonadogenesis in chicken embryos. (2016)
  • Author(s): Yoshino, T., Murai, H., and Saito, D.
  • Journal Title: Nat. Commun. Volume: 7 Issue: 1 Pages: 12561-12561
  • DOI: 10.1038/ncomms12561
  • NAID: 120006345029
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Sympatho-adrenal morphogenesis regulated by the dorsal aorta. (2015)
  • Author(s): Saito, D. and Takahashi, Y.
  • Journal Title: Mechanism of Development Volume: S0925-4773(15) Pages: 30013-30017
  • DOI: 10.1016/j.mod.2015.07.011
  • NAID: 120005980828
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] AP-2β is a transcriptional regulator for determination of digit length in tetrapods. (2015)
  • Author(s): Seki R, Kitajima K, Matsubara H, Suzuki T, Saito D, Yokoyama H, Tamura K.
  • Journal Title: Dev Biol. Volume: 407 Issue: 1 Pages: 75-89
  • DOI: 10.1016/j.ydbio.2015.08.006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Angiogenesis in the developing spinal cord: Blood vessel exclusion from neural progenitor region is mediated by VEGF and its antagonists. (2014)
  • Author(s): Takahashi, T., Takase, Y., Yoshino, T., Saito, D., Tadokoro, R. and *Takahashi, Y.
  • Journal Title: PLOS ONE Volume: 10(1) Issue: 1 Pages: e0116119-e0116119
  • DOI: 10.1371/journal.pone.0116119
  • NAID: 120005998022
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Germ Cell Extravasation Mechanism in Avian Embryo. (2017)
  • Author(s): Saito, D.
  • Organizer: 14th International conference on flow dynamics
  • Int'l Joint Research / Invited
• [Presentation] Cell stiffness is critical for germ cell migration in avian embryo. (2017)
  • Author(s): Saito, D.
  • Organizer: International Forum on Avian Germplasm and Genome Editing 2017
  • Int'l Joint Research / Invited
• [Presentation] The establishment of quail primordial germ cell culture system. (2017)
  • Author(s): Saito, D.
  • Organizer: 日本発生生物学会第50回大会
  • Int'l Joint Research
• [Presentation] 「鳥類始原生殖細胞の血管内移動における細胞弾性の役割」 (2017)
  • Author(s): 齋藤大介
  • Organizer: 日本動物学会第88回大会
• [Presentation] Avian primordial germ cell migration in the blood stream. (2015)
  • Author(s): Saito, D.
  • Organizer: “Cell- and tissue communication in organogenesis: cutting edge approaches” The Fondation des Treilles
  • Place of Presentation: Les Arcs-Draguignan, France
  • Year and Date: 2015-09-21
  • Int'l Joint Research / Invited
• [Presentation] Gonad and adrenal cortex derive from different origins within the coelom. (2015)
  • Author(s): Saito, D., Takahashi, Y.
  • Organizer: 日本発生生物学会第48回大会
  • Place of Presentation: 茨城県つくば市
  • Year and Date: 2015-06-02
• [Remarks] 『Nature Communications』に論文掲載、および報道発表
  • URL: http://www.fris.tohoku.ac.jp/fris/activity/topics/2016/t2016_022.html
• [Remarks] 胎仔で生殖腺形成を開始させている仕組みに初めて迫る
  • URL: http://www.tohoku.ac.jp/japanese/2016/08/award20160826-01.html