Kyoto Sangyo University ~ Organogenesis Lab (Shiratori Lab)

 

Research projects

Several visceral organs are left-right (L-R) asymmetrically located in vertebrates. In embryonic development, the visceral organs are L-R symmetrically initiated, and then their shape is asymmetrically changed through asymmetric gene expression. We want to know the mechanism for the generation of L-R asymmetry.

How is the asymmetric expression of the genes regulated? 

How is the shape of the visceral organs changed?

We observe the morphogenesis of each organ in detail, focusing on the differences between left and right in cell shape, cell migration, cell proliferation, and cell death, and analyze the roles and transcriptional mechanisms of the genes that are asymmetrically expressed using mutant and transgenic mice.

LR1 is an extracellular matrix protein and is L-R asymmetrically expressed in the mouse embryo. The LR1 mutant mice had shown L-R defects, while some of the homozygotes had been early embryonic lethal.

 We also analyze the roles of amino acid metabolizing enzymes, Pycr2 and Shmt2. We reported that the Pycr2 KO mice showed a premature aging-like phenotype, and Pycr2 regulates Shmt2 in the mouse brain (Escande-Beillard N. et al., 2020). The Shmt2 KO mouse is embryonic lethal, suggesting Shmt2 is essential for mouse embryogenesis. We want to clarify the mechanisms of the symptoms in these KO mice using mutant and transgenic mice.

 

 

Members

Prof. Hideataka Shiratori (D.V.M., Ph D)

 

Graduate students

Rina Kataoka (M1)

Ami Matsumoto (M1)

 

Undergraduates

Tomoya Irie (B4)

Kota Sagane (B4)

Reiji Yoshimoto (B4)

Shuri Inoue (B3)

Riko Iwata (B3)

Miu Ueda (B3)

Koki Kuroyabu (B3)

Aya Fujimoto (B3)

 

Research papers

Loss of PYCR2 Causes Neurodegeneration by Increasing Cerebral Glycine Levels via SHMT2.

Escande-Beillard N, Loh A, Saleem SN, Kanata K, Hashimoto Y, Altunoglu U, Metoska A, Grandjean J, Ng FM, Pomp O, Baburajendran N, Wong J, Hill J, Beillard E, Cozzone P, Zaki M, Kayserili H, Hamada H, Shiratori H, Reversade B.

(Neuron. 2020 Jul 8;107(1):82-94.e6.)

 

Role of Ca2+ transients at the node of the mouse embryo in breaking of left-right symmetry.

Mizuno K, Shiozawa K, Katoh TA, Minegishi K, Ide T, Ikawa Y, Nishimura H, Takaoka K, Itabashi T, Iwane AH, Nakai J, Shiratori H, Hamada H.

(Sci Adv. 2020 Jul 22;6(30):eaba1195.)

 

TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization.

Wallmeier J, Shiratori H, Dougherty GW, Edelbusch C, Hjeij R, Loges NT, Menchen T, Olbrich H, Pennekamp P, Raidt J, Werner C, Minegishi K, Shinohara K, Asai Y, Takaoka K, Lee C, Griese M, Memari Y, Durbin R, Kolb-Kokocinski A, Sauer S, Wallingford JB, Hamada H, Omran H.

(Am J Hum Genet. 2016 Aug 4;99(2):460-9.)

 

A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking.

Minegishi K, Hashimoto M, Ajima R, Takaoka K, Shinohara K, Ikawa Y, Nishimura H, McMahon AP, Willert K, Okada Y, Sasaki H, Shi D, Fujimori T, Ohtsuka T, Igarashi Y, Yamaguchi TP, Shimono A, Shiratori H, Hamada H.

(Dev Cell. 2017 Mar 13;40(5):439-452.e4.)

 

TGFβ signaling in establishing left-right asymmetry.

Shiratori H, Hamada H.

(Semin Cell Dev Biol. 2014 32:80-4.)

 

Cilia at the node of mouse embryos sense fluid flow for left-right determination via Pkd2.

Yoshiba S, Shiratori H, Kuo IY, Kawasumi A, Shinohara K, Nonaka S, Asai Y, Sasaki G, Belo JA, Sasaki H, Nakai J, Dworniczak B, Ehrlich BE, Pennekamp P, Hamada H.

(Science. 2012 Oct 12;338(6104):226-31.)

 

Determination of left-right patterning of the mouse embryo by artificial nodal flow.

 Nonaka S, Shiratori H, Saijoh Y, Hamada H.

(Nature. 2002 Jul 4;418(6893):96-9.)

 

Self-regulated left-right asymmetric expression of Pitx2c in the developing mouse limb.

 Shiratori H, Yashiro K, Iwai N, Oki S, Minegishi K, Ikawa Y, Kanata K, Hamada H.

(Dev Biol. 2014 Nov 15;395(2):331-41.)

 

Haemodynamics determined by a genetic programme govern asymmetric development of the aortic arch.

 Yashiro K, Shiratori H, Hamada H.

(Nature. 2007 Nov 8;450(7167):285-8.)

 

Conserved regulation and role of Pitx2 in situs-specific morphogenesis of visceral organs.

 Shiratori H, Yashiro K, Shen MM, Hamada H.

(Development. 2006 Aug;133(15):3015-25.)

 

Two-step regulation of left-right asymmetric expression of Pitx2: initiation by nodal signaling and maintenance by Nkx2.

 Shiratori H, Sakuma R, Watanabe M, Hashiguchi H, Mochida K, Sakai Y, Nishino J, Saijoh Y, Whitman M, Hamada H.

(Mol Cell. 2001 Jan;7(1):137-49.)