This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nosaka, T.
Right arrow Articles by Kitamura, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nosaka, T.
Right arrow Articles by Kitamura, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2003, p. 2969-2980, Vol. 23, No. 8
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.8.2969-2980.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Mammalian Twisted Gastrulation Is Essential for Skeleto-Lymphogenesis

Tetsuya Nosaka,1* Sumiyo Morita,1,{dagger} Hidetomo Kitamura,2 Hideaki Nakajima,3 Fumi Shibata,1 Yoshihiro Morikawa,4 Yuki Kataoka,5 Yasuhiro Ebihara,3 Toshiyuki Kawashima,1 Tsuneo Itoh,2 Katsutoshi Ozaki,1 Emiko Senba,4 Kohichiro Tsuji,3 Fusao Makishima,2 Nobuaki Yoshida,5 and Toshio Kitamura3

Division of Hematopoietic Factors,1 Division of Cellular Therapy, Advanced Clinical Research Center,3 Laboratory of Gene Expression and Regulation, Center for Experimental Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639,5 Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd., Shizuoka 412-8513,2 Department of Anatomy and Neurobiology, Wakayama Medical School, Wakayama 641-8509, Japan4

Received 27 August 2002/ Returned for modification 4 November 2002/ Accepted 30 January 2003

Dorsoventral patterning depends on the local concentrations of the morphogens. Twisted gastrulation (TSG) regulates the extracellular availability of a mesoderm inducer, bone morphogenetic protein 4 (BMP-4). However, TSG function in vivo is still unclear. We isolated a TSG cDNA as a secreted molecule from the mouse aorta-gonad-mesonephros region. Here we show that TSG-deficient mice were born healthy, but more than half of the neonatal pups showed severe growth retardation shortly after birth and displayed dwarfism with delayed endochondral ossification and lymphopenia, followed by death within a month. TSG-deficient thymus was atrophic, and phosphorylation of SMAD1 was augmented in the thymocytes, suggesting enhanced BMP-4 signaling in the thymus. Since BMP-4 promotes skeletogenesis and inhibits thymus development, our findings suggest that TSG acts as both a BMP-4 agonist in skeletogenesis and a BMP-4 antagonist in T-cell development. Although lymphopenia in TSG-deficient mice would partly be ascribed to systemic effects of runtiness and wasting, our findings may also provide a clue for understanding the pathogenesis of human dwarfism with combined immunodeficiency.

* Corresponding author. Mailing address: Division of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-5449-5399. Fax: 81-3-5449-5453. E-mail: tenosaka{at}ims.u-tokyo.ac.jp.

{dagger} Present address: Gene Research Center, Gunma University, Maebashi 371-8511, Japan.

Molecular and Cellular Biology, April 2003, p. 2969-2980, Vol. 23, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.8.2969-2980.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Larman, B. W., Karolak, M. J., Adams, D. C., Oxburgh, L. (2009). Chordin-like 1 and Twisted Gastrulation 1 Regulate BMP Signaling following Kidney Injury. J. Am. Soc. Nephrol. 20: 1020-1031 [Abstract] [Full Text]  
  • Smerdel-Ramoya, A., Zanotti, S., Stadmeyer, L., Durant, D., Canalis, E. (2008). Skeletal Overexpression of Connective Tissue Growth Factor Impairs Bone Formation and Causes Osteopenia. Endocrinology 149: 4374-4381 [Abstract] [Full Text]  
  • Smerdel-Ramoya, A., Zanotti, S., Deregowski, V., Canalis, E. (2008). Connective Tissue Growth Factor Enhances Osteoblastogenesis in Vitro. J. Biol. Chem. 283: 22690-22699 [Abstract] [Full Text]  
  • Zhang, J.-L., Huang, Y., Qiu, L.-Y., Nickel, J., Sebald, W. (2007). von Willebrand Factor Type C Domain-containing Proteins Regulate Bone Morphogenetic Protein Signaling through Different Recognition Mechanisms. J. Biol. Chem. 282: 20002-20014 [Abstract] [Full Text]  
  • Rydziel, S., Stadmeyer, L., Zanotti, S., Durant, D., Smerdel-Ramoya, A., Canalis, E. (2007). Nephroblastoma Overexpressed (Nov) Inhibits Osteoblastogenesis and Causes Osteopenia. J. Biol. Chem. 282: 19762-19772 [Abstract] [Full Text]  
  • Rossi, S. W., Jeker, L. T., Ueno, T., Kuse, S., Keller, M. P., Zuklys, S., Gudkov, A. V., Takahama, Y., Krenger, W., Blazar, B. R., Hollander, G. A. (2007). Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells. Blood 109: 3803-3811 [Abstract] [Full Text]  
  • Ikeya, M., Kawada, M., Kiyonari, H., Sasai, N., Nakao, K., Furuta, Y., Sasai, Y. (2006). Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis. Development 133: 4463-4473 [Abstract] [Full Text]  
  • Schmidl, M., Adam, N., Surmann-Schmitt, C., Hattori, T., Stock, M., Dietz, U., de Crombrugghe, B., Poschl, E., von der Mark, K. (2006). Twisted Gastrulation Modulates Bone Morphogenetic Protein-induced Collagen II and X Expression in Chondrocytes in Vitro and in Vivo. J. Biol. Chem. 281: 31790-31800 [Abstract] [Full Text]  
  • Ono, R., Ihara, M., Nakajima, H., Ozaki, K., Kataoka-Fujiwara, Y., Taki, T., Nagata, K.-i., Inagaki, M., Yoshida, N., Kitamura, T., Hayashi, Y., Kinoshita, M., Nosaka, T. (2005). Disruption of Sept6, a Fusion Partner Gene of MLL, Does Not Affect Ontogeny, Leukemogenesis Induced by MLL-SEPT6, or Phenotype Induced by the Loss of Sept4. Mol. Cell. Biol. 25: 10965-10978 [Abstract] [Full Text]  
  • Bleul, C. C., Boehm, T. (2005). BMP Signaling Is Required for Normal Thymus Development. J. Immunol. 175: 5213-5221 [Abstract] [Full Text]  
  • Gazzerro, E., Deregowski, V., Vaira, S., Canalis, E. (2005). Overexpression of Twisted Gastrulation Inhibits Bone Morphogenetic Protein Action and Prevents Osteoblast Cell Differentiation in Vitro. Endocrinology 146: 3875-3882 [Abstract] [Full Text]  
  • Urano, A., Endoh, M., Wada, T., Morikawa, Y., Itoh, M., Kataoka, Y., Taki, T., Akazawa, H., Nakajima, H., Komuro, I., Yoshida, N., Hayashi, Y., Handa, H., Kitamura, T., Nosaka, T. (2005). Infertility with Defective Spermiogenesis in Mice Lacking AF5q31, the Target of Chromosomal Translocation in Human Infant Leukemia. Mol. Cell. Biol. 25: 6834-6845 [Abstract] [Full Text]  
  • Zakin, L., Reversade, B., Kuroda, H., Lyons, K. M., De Robertis, E. M. (2005). Sirenomelia in Bmp7 and Tsg compound mutant mice: requirement for Bmp signaling in the development of ventral posterior mesoderm. Development 132: 2489-2499 [Abstract] [Full Text]  
  • Little, S. C., Mullins, M. C. (2004). Twisted gastrulation promotes BMP signaling in zebrafish dorsal-ventral axial patterning. Development 131: 5825-5835 [Abstract] [Full Text]  
  • Zakin, L., De Robertis, E. M. (2004). Inactivation of mouse Twisted gastrulation reveals its role in promoting Bmp4 activity during forebrain development. Development 131: 413-424 [Abstract] [Full Text]  
  • Tsai, P. T., Lee, R. A., Wu, H. (2003). BMP4 acts upstream of FGF in modulating thymic stroma and regulating thymopoiesis. Blood 102: 3947-3953 [Abstract] [Full Text]  
  • Blitz, I. L., Cho, K. W. Y., Chang, C. (2003). Twisted gastrulation loss-of-function analyses support its role as a BMP inhibitor during early Xenopus embryogenesis. Development 130: 4975-4988 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»