Yoichi Kato, M.D., Ph.D.
Nagoya City University Medical School, Japan
Florida State University
College of Medicine
1115 West Call Street
Tallahassee, FL 32306-4300
Office: (850) 645-1481, MSR 3300-K
Lab: (850) 645-2929, MSR 3310-L
We focus on dissecting the roles of the signal transduction pathways during development.
In my lab, two main projects are going on:
The molecular mechanisms of cilia formation during development
The cilium is a small cellular organelle which broadly exists throughout the human body in either motile or immotile form. Motile cilia generate force by beating for directional fluid movement, whereas primary (non-motile) cilia are involved in sensory processes and cellular signaling (Figure 1). Disruption of ciliary structure and/or function in humans causes pleiotropic disorders, called ciliopathies. Although a certain length of motile cilia is important for their normal function, the molecular mechanism that regulates cilia length still remains to be explored.
We recently found that blocking the Smad2/3-dependent TGF-β (Xnr1 and Derrière) pathway in Xenopus embryos shortened motile cilia in several tissues (Figure 2). We further found that the role of TGF-β signaling seems to be independent of known mechanisms that regulate cilia formation including ciliary length control. However, the mechanism that is regulated by TGF-β signaling still remains unknown. To understand the mechanism of ciliary length control, we will analyze this mechanism by using state-of-art technologies such as next generation sequencing and proteomics.
Identifying chemical compounds that regulate neuronal differentiation
Stem cell therapy holds considerable promise for the treatment of degenerative diseases. Stem cells are differentiated into required cell types to replace non-functional tissues in degenerative diseases and injuries to functional normal tissues. Stem cell differentiation is regulated by both intrinsic regulators and the extracellular environment, and can be controlled ex vivo by cell culture manipulation with ‘‘cocktails’’ of growth factors, signaling molecules, and/or by genetic manipulation. A challenge to disseminate stem cell therapy is to establish inexpensive and safe methods by which stem cells are differentiated into required cell types. However, purified growth factors are still expensive,
and risk of genetic manipulation to recipients with transplantation of these cells is also considerable.
Since human or mouse embryonic stem cells have been hampered by multiple technical challenges, we are using Xenopus embryos for high-throughput screening (HTS) of chemical compound libraries to identify new chemical compounds. We have identified some compounds to control neuronal differentiation (Figure 3).
Current Lab Members
- Akiko Kato: Lab Assistant
- Tözser J, Earwood R, Kato A, Brown J, Tanaka K, Didier R, Megraw T, Blum M, Kato Y. Activation of TGF-β signaling is required to control the length of motile cilia. Cell Rep 2015, 11: 1-8. *co- corresponding authors.
- Manojlovic Z, Earwood R, Kato A, Stefanovic B*, Kato Y*. RFX7 is required for the formation of cilia in the neural tube. Mech Dev 2014, 32:28-37. *co- corresponding authors.
- Tanaka K, Kato A, Angelocci C, Watanabe M, Kato Y. A potential molecular pathogenesis of cardiac/laterality defects in Oculo-Facio-Cardio-Dental syndrome. Dev Biol 2014, 387:28-36.
- Xu Y, Xu C, Kato A, Tempel W, Abreu JG, Bian C, Hu Y, Hu D, Zhao B, Cerovina T, Diao J, Wu F, He HH, Cui Q, Clark E, Ma C, Barbara A, Veenstra GJ, Xu G, Kaiser UB, Liu XS, Sugrue SP, He X, Min J*, Kato Y*, Shi YG*. Tet3 CXXC Domain and Dioxygenase Activity Cooperatively Regulate Key Genes for Xenopus Eye and Neural Development. Cell 2012, 151:1200-13. *co- corresponding authors.
- Kato Y. The multiple roles of Notch signaling during left-right patterning. Cell Mol Life Sci. 2011, 68:2555–2567.
- Sakano D, Kato A, Parikh N, McKnight K, Terry D, Stefanovic B and Kato Y. BCL6 canalizes Notch-dependent transcription, excluding Mastermind-like1 from selected target genes during left-right patterning. Developmental Cell 2010, 18: 450–462.
- Kiyota T, Kato A, Altmann CR, Kato Y. The POU homeobox protein Oct-1 regulates radial glia differentiation downstream of Notch signaling. Developmental Biology 2008, 315: 579-592.
- Kiyota T, Kato A, Kato Y. Ets-1 regulates radial glia formation during vertebrate embryogenesis. Organogenesis 2007, 3: 93-101.
- Kato Y, Habas R, Katsuyama Y, Naar AM, He X. A component of the ARC/Mediator complex required for TGF beta/Nodal signalling. Nature. 2002 418:641-6.
- Kato Y, Shi Y, He X.Neuralization of the Xenopus embryo by inhibition of p300/ CREB-binding protein function. J Neurosci. 1999 19:9364-73.