Identification of the gravity sensory system in bone homeostasis in medaka – Publicly Invited Research
- A02 Shinohara
- A02 Maekawa
- A02 Ohgami
- A02 Nishimura
- A02 Kawano
- A02 Iwase
- A02 Furuichi
- A02 Myung
- A02 Kitamura
|Research Subject||Elucidation of the molecular mechanism underlying gravity-YAP-mediated 3D organogenesis -Toward generating a complex 3D organ in microgravity-|
|Research Group Leader||
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