Research summary (Hideho Uchiyama)

Amphibians are useful materials in developmental research. It is because their eggs are so big that we can perform injection or dissection experiments easily. Cleavages, axes formation, induction, gastrulation, cell differentiation have been well studied in these animals. Genome sequencing has also been greatly proceeded. I am analyzing mesoderm differentiation in Xenopus, with special interests in its relation to T-box transcription factors. These factors begin to be transcribed very early after mesoderm-induction by FGF or activin-related signals, and trigger cell differentiation as master control genes.

One of my target Tbx6, a T-box transcription factor that is expressed in nascent latero-ventral mesoderm, elicits lateral plate-like cell differentiations when overexpressed in animal cap cells. It also triggers muscular differentiation when overexpressed together with noggin, one of the BMP antagonists, in animal cap cells. When we knockdown tbx6 in embryos by injecting an antisense morpholino oligo, metameric patterns in somites and formation of ventral body wall muscles become defective, suggesting its involvement in the formation of these tissues. Tbx6 triggers transctiption of pMesogenins, bHLH class of transcription factors, which are involved in the differentiation of ventral body wall muscles.

(left panel) In situ hybridization of two T-box genes: Tbx6 (turquoise) and Tbx6r (dark blue) in the neurula embryo (posterior view). Tbx6r-expressing area is confined to dorsolateral positions and entirely included in the wider Tbx6-expressing area around the blastopore.

As for metamerism in somitogenesis, Tbx6 triggers transctiptions of bowline and ledgerline, two counterparts of mouse ripply family of transctiption factors. These are involved in the formation of repeated patterns, whereas ledgerline suppresses transctiption of tbx6 in cooperation with a co-repressor Groucho in a negative feedback manner, restricting the expression of Tbx6 only in the most posterior part of mesoderm.




Another subject of study is cell differentiation of mammalian pleuripotent stem cells. This work is operated in collaboration with prof. Asashima (formerly in Tokyo Univ., now in AIST, National Institute of Advanced Industrial Science and Technology in Tsukuba). Ongoing studies include the differentiation of neural crest cells from mouse ES cells in a serum- or feeder layer-free conditions.






　< Recent research themes >

  1. Analysis of the role of T-box transcription factors in development
  2. Search for target genes for T-box transcription factors.
  3. Differentiation in vitro of mammalian pleuripotent stem cells.

------　Recent Publishing　------

1）　Aihara Y, Hayashi Y, Hirata M, Ariki N, Shibata S, Nagoshi N, Nakanishi M, Ohnuma K, Warashina M, Michiue T,
　　 Uchiyama H, Okano H, Asashima M and Furue MK
　　　Induction of neural crest cells from mouse embryonic stem cells in a serum-free monolayer culture.
　　　Int. J. Dev. Biol., 54, 1287-1294, 2010.

2)　Konno, M.,, Hamazaki, T. S., Fukuda, S., Tokuhara, M., Uchiyama, H., Okazawa, H., Okochi, H., Asashima, M.
　　　Efficiently Differentiating Vascular Endothelial Cells from Adipose Tissue Derived Mesenchymal Stem Cells in Serum-Free Culture.
　　　Biochem. Biophys. Res. Commun., 400, 461-465, 2010.

3) Tazumi, S., Yabe, S., and Uchiyama, H.
　　Paraxial T-box genes, Tbx6 and Tbx1, are required for cranial chondrogenesis and myogenesis.
　　Devl. Biol., in press.
　　Accession number of the partial cDNA of X. laevis pcdh18: AB573177

4)　Kawsar, S.M.A., R. Matsumoto, Y. Fujii, H. Yasumitsu, H. Uchiyama, M. Hosono, K. Nitta, J. Hamako, T. Matsui, N. Kojima, and Y. Ozeki.
　　Glycan-binding profile and cell adhesion activity of American bullfrog (Rana catesbeiana) oocyte galectin-1.
　　Prot. Peptide Lett. 16, 677-684, 2009.

5) Hitachi, K., Danno, H., Tazumi S., Aihara Y., Uchiyama, H., Okabayashi, K., Kondow, A., and Asashima, M.
　　The Xenopus Bowline/Ripply family proteins negatively regulate the transcriptional activity of T-box transcription factors.
　　Int. J. Dev. Biol. 53, 631-639, 2009.

6) Tazumi, S., S. Yabe, J. Yokoyama, Y. Aihara, and H. Uchiyama.
　　pMesogenin1 and 2 function directly downstream of Xtbx6 in Xenopus somitogenesis and myogenesis.
　　Dev. Dyn. 237, 3749-3761, 2008.
　　Dev. Dyn. 238, issue2, page fvii, DD Artpix, 2009
　　Accession number of pMesogenin2 genomic DNA: AB462327.
　　Accession number of Xtbx6 exon1-exon2 genomic DNA: AB462326.

7) Hitachi K., Danno H., Kondow A., Ohnuma K., Uchiyama H., Ishiura S., Kurisaki A, and Asashima M.
　　Physical interaction between Tbx6 and mespb is indispensable for the activation of bowline expression during Xenopus somitogenesis.
　　Biochem. Biophys. Res. Commun., 372, 607-612, 2008.

8) Hitachi K., Kondow A., Danno H., Inui M., Uchiyama H., and Asashima M.
　　Tbx6, Thylacine1, and E47 synergistically activate bowline expression in Xenopus somitogenesis.
　　Devl. Biol., 313, 816-828, 2008.

9) Yabe S., Tazumi S., Yokoyama J., and Uchiyama, H.
　　Xtbx6r, a novel T-box gene expressed in the paraxial mesoderm, has anterior neural-inducing activity.
　　Int. J. Dev. Biol., 50, 681-689, 2006.
　　Accession number of Xtbx6r cDNA:　AB284536

10) Murakami R., Okumura T., and Uchiyama H.
　　GATA factors as key regulatory molecule in the development of Drosophila endoderm.
　　Dev. Growth Differ. 47, 581-589, 2005.

11) Hamaguchi T., S. Yabe, H. Uchiyama, and R. Murakami.
　　Drosophila Tbx6-related gene, Dorsocross, mediates high levels of Dpp/Scw signal required for the development of amnioserosa and wing discs.
　　Devl. Biol. 265, 355-368, 2004.

12) Uchiyama H., T. Kobayashi, A. Yamashita, S. Ohno and S. Yabe.
　　Corrigendum: Cloning and characterization of the T-box gene Tbx6 in Xenopus laevis.
　　Develop Growth Differ. 44, 95-96, 2002.
　　Uchiyama, H., T．Kobayashi，A．Yamashita，S. Ohno, and S. Yabe.
　　Cloning and characterization of a T-box gene Tbx6 in Xenopus laevis.
　　Develop. Growth Differ. 43, 657-669, 2001.
　　Accession number of Xtbx6 cDNA:　AB091393

13) Uchiyama, H., A. Koda, S. Komazaki, M. Oyama, and S. Kikuyama.
　　Occurrence of immunoreactive activin/inhibin βB in thyrotropes and gonadotropes in the bullfrog pituitary: possible paracrine/autocrine effects of activin B on gonadotropin secretion.
　　Gen. Comp. Endocrinol. 118, 68-76 (2000).

14)　Koda A., K. Yamamoto, H. Uchiyama, H. Vaudry, and S. Kikuyama.
　　Effect of activin A and follistatin on the release of pituitary hormones in the bullfrog Rana Catesbeiana.
　　Zool. Sci. 17, 971-975 (2000)

15) Yamamoto T., S. Iemura, S. Takagi, H. Uchiyama, S. Shimasaki, H. Sugino and N. Ueno.
　　Direct binding of follistatin to BMPs inhibits ventral and epidermal cell fates in early Xenopus embryo.
　　Proc. Natl. Acad. Sci. USA 95, 9337-9342 (1998).


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