Xenopus tropicalis nodal-related gene 3 regulates BMP signaling: an essential role for the pro-region.
In vertebrates, nodal-related genes are crucial for specifying mesendodermal cell fates. Six nodal-related genes have been identified in Xenopus, but only one, nodal, has been identified in the mouse. The Xenopus nodal-related gene 3 (Xnr3), however, lacks the mesoderm-inducing activity of the other five nodal-related genes in Xenopus, and can directly induce neural tissue in animal caps by antagonizing BMP signals. In this study, we isolated three clones of the Xenopus (Silurana) tropicalis nodal-related gene 3 (Xtnr3) and analyzed their function. The Xtnr3 genes show high homology to Xnr3 and have the same activity. Southern blot and genomic PCR analyses indicate that the X. tropicalis genome has duplications in the Xtnr3 gene sequences and our three clones represent separate gene loci. We also found a partial clone of Xtnr3 that coded for the N-terminal part of its pro-region. Surprisingly, this sequence also induced neural tissue by antagonizing BMP signals, and its coded protein physically associated with BMP4 mature protein. Furthermore, we showed that the pro-region of Xnr5 has the same activity. Together, these findings indicate that the pro-region of nodal-related genes acts antagonistically towards BMP signals, which identifies a novel mechanism for the inhibition of BMP signaling.
Haramoto
Yoshikazu
Y
Department of Life Sciences (Biology), The University of Tokyo, Meguro, Tokyo 153-8902, Japan.
Tanegashima
Kousuke
K
Onuma
Yasuko
Y
Takahashi
Shuji
S
Sekizaki
Hiroyuki
H
Asashima
Makoto
M
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000502:physiology; D017931:DNA Primers; D004627:Embryonic Induction / Q000502:physiology*; D017403:In Situ Hybridization; D008845:Microinjections; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C094620:nodal3.1 protein, Xenopus