Identification of the gravity sensory system in bone homeostasis in medaka – Publicly Invited Research

  1. A01 Akiyama
  2. A01 Ochi
  3. A01 Chatani
  4. A01 Seiki
  5. A01 Nikawa
  6. A01 Kawakami
  7. A01 Tomita
  8. A01 Honda
  1. A02 Shinohara
  2. A02 Maekawa
  3. A02 Ohgami
  4. A02 Nishimura
  5. A02 Kawano
  6. A02 Iwase
  7. A02 Furuichi
  8. A02 Myung
  9. A02 Kitamura
  1. A03 Nakamura
  2. A03 Harada
  3. A03 Ide
  4. A03 Shirai
  5. A03 Kakinuma
  1. B01 Lazarus
  2. B01 Miwa
  3. B01 Kunieda
  4. B01 Shimada
  5. B01 Kitaya
  6. B01 Sawano
Research Subject Elucidation of the molecular mechanism underlying gravity-YAP-mediated 3D organogenesis -Toward generating a complex 3D organ in microgravity-
Research Group Leader
Makoto Furutani-Seiki
Research Collaborator(s)
  • Takao Kitagawa
    Assistant professor, Systems Biochemistry in Pathology and Regeneration, Yamaguchi University Graduate School of Medicine
  • Yoichi Asaoka
    University lecturer, Genomics and Molecularl Analysis, Yamaguchi University Graduate School of Medicine

Vision requires the lens to be centered in the eye cup, both of whose tissues have unique 3D shapes. However, a genetic mechanism that regulates correct tissue/organ shape and alignment had never been suspected. Our analysis of “hirame” medaka fish mutants with a flat body and organs revealed that to in order to withstand gravity, YAP controls cellular mechanical forces that regulate 3D tissue shape and alignment of tissues to generate 3D organs (Fig. 1., Porazinski et al., Nature, 521, 2015).
A structure that resembles a human organ (called organoid) can be generated from ES and iPS cells (Takebe et al., Cell Stem Cell, 16, 2015). However, such organoids are too small for regeneration therapy. As the activation of YAP can expand organ size 3-5 times in a week (Fig. 2 (A); Dong et al., Cell, 130. 2007)), we will develop a method of expanding 3D organoids by activating YAP through gravity-YAP-mediated 3D organogenesis signaling (Fig. 2 (B)).
Our research is intended to elucidate the molecular mechanism underlying gravity-YAP signaling, and to facilitate the generation and expansion of 3D complex organoids by manipulating gravity.

Fig. 1. Gravity activating YAP control of 3D organ formation by tissue tension-mediated 3D tissue formation and alignment

Fig. 2. (A) YAP unique function to expand organ size; (B) Manipulation of gravity to expand human organoids