The Extracellular Adenosine Deaminase Growth Factor, ADGF/CECR1, Plays a Role in Xenopus Embryogenesis via the Adenosine/P1 Receptor*
- Ryoko Iijima ‡ § ¶ 1 ,
- Takekazu Kunieda § 1 ,
- Shinji Yamaguchi ‡ ∥ 1 ,
- Hiroko Kamigaki ∥ ,
- Ikuko Fujii-Taira ‡ ¶ ,
- Kazuhisa Sekimizu ‡ ,
- Takeo Kubo § ,
- Shunji Natori ¶ and
- Koichi J. Homma ‡ ∥ 2
- ‡Graduate School of Pharmaceutical Sciences, and §Graduate School of Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, the ¶Natori Special Laboratory, The Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-0198, and the ∥Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa 229-0195, Japan
- 2 To whom correspondence should be addressed: Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa 229-0195, Japan. Tel.: 81-42-685-3739; Fax: 81-42-685-3738; E-mail: homma-kj{at}umin.ac.jp.
Abstract
Adenosine deaminase-related growth factors (ADGF), also known as CECR1 in vertebrates, are a novel family of growth factors with sequence similarity to classical cellular adenosine deaminase. Although genes for ADGF/CECR1 have been identified in both invertebrates as well as vertebrates, their in vivo functions in vertebrates remain unknown. We isolated cDNA clones for two cerc 1s from Xenopus laevis. Both recombinant Xenopus CECR1s exhibited adenosine deaminase and growth factor activity, and the adenosine deaminase activity was found to be indispensable for growth factor activity. The Xenopus cerc 1s are expressed in the somites, pronephros, eyes, cement gland, neural tube, and neural floor plate of the embryos. Knock-down of these two genes using morpholino oligonucleotides caused a reduction in the body size and abnormalities of the body axis in the Xenopus embryos, accompanied by selective changes in the expression of developmental marker genes. Injection of adenosine, agonists for adenosine/P1 receptors, or adenosine deaminase inhibitor into late gastrula archenteron embryos resulted in developmental defects similar to those caused by morpholino oligonucleotide injection. These results show, for the first time, the involvement of CECR1s via the adenosine/P1 receptors in vertebrate embryogenesis via regulation of extracellular adenosine concentrations.
Footnotes
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↵ 3 The abbreviations used are: ADGF, adenosine deaminase-related growth factor; ADA, adenosine deaminase; CECR1, cat eye syndrome critical region candidate 1; DCF, 2′-deoxycoformycin; EHNA, erythro-9-(2-hydroxy-3-nonyl)-adenine hydrochloride; IDGF, insect-derived growth factor; RT, reverse transcriptase; MO, morpholino oligonucleotide.
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The nucleotide sequence(s) reported in this paper has been submitted to the Gen-Bank™/EBI Data Bank with accession number(s) AY986978 and AY986979.
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↵* This work was supported by Grants-in-aid for Scientific Research from the Japan Society for the Promotion of Science (to K. J. H.), the Ministry of Education, Science, Sports and Culture of Japan (to S. Y.), the Naito Foundation (to K. J. H.), the Japan Foundation of Applied Enzymology (to K. J. H.), the Uehara Memorial Foundation (to S. Y.), the Sagawa Foundation for Promotion of Cancer Research (to S. Y.), and the Core Research for Evolutional Science and Technology of the Japan Science and Technology Corporation (to S. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 These authors contributed equally to this work.
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- Received November 12, 2007.
- The American Society for Biochemistry and Molecular Biology, Inc.
