The extracellular adenosine deaminase growth factor, ADGF/CECR1, plays a role in Xenopus embryogenesis via the adenosine/P1 receptor.
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.
Iijima
Ryoko
R
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kunieda
Takekazu
T
Yamaguchi
Shinji
S
Kamigaki
Hiroko
H
Fujii-Taira
Ikuko
I
Sekimizu
Kazuhisa
K
Kubo
Takeo
T
Natori
Shunji
S
Homma
Koichi J
KJ
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D049628:Body Size / Q000187:drug effects / Q000502:physiology; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology*; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009928:Organ Specificity / Q000502:physiology; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D036341:Intercellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D029867:Xenopus Proteins; D000243:Adenosine Deaminase; C527536:CECR1 protein, Xenopus; D000241:Adenosine