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.
①How is the asymmetric
expression of the genes regulated?
②How 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.
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.
Sci
Adv. 2020 Jul 22;6(30):eaba1195.)
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.)
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.)
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.)