Xantivin suppresses the activity of EGF-CFC genes to regulate nodal signaling.
Lefty, antivin and related genes act in a feedback inhibition mechanism for nodal signaling at a number of stages of vertebrate embryogenesis. To analyze the function of the feedback inhibitor of nodal signaling, Xantivin in Xenopus embryos, we designed a morpholino antisense oligonucleotide (XatvMO) for this gene. XatvMO caused the expansion of mesodermal tissue and head defects. XatvMO-injected gastrulae showed up-regulated expression of the mesodermal markers Xbra, Xwnt8, Xnot, and Chordin, suggesting expansion of the trunk-tail organizer. As expected, depletion of Xantivin also up-regulated nodal signaling as confirmed by the enhanced ectopic expression of Xantivin mRNA, a known target gene of nodal signaling. Furthermore, we investigated the relationship between Xantivin and the EGF-CFC gene FRL-1, which is a component of the nodal receptor. In animal cap assays, FRL-1 could not induce expression of nodal-responsive genes, but could up-regulate expression of these genes when FRL-1 was coinjected with a low dose of Xnr1; coinjection of Xantivin suppressed this up-regulation by FRL-1. We also found that Xantivin can rescue the caudalized phenotype induced by overexpression of FRL-1. Co-immunoprecipitation assays showed that Xantivin interacted with the EGF-CFC proteins, FRL-1 and cripto. Taken together, these results suggest that Xantivin opposes the activity of EGF-CFC genes and thereby antagonizes nodal signaling.
Department of Life Sciences (Biology), University of Tokyo, Komaba, Tokyo, Japan.
Kousuke
K
Tanegashima
Yoshikazu
Y
Haramoto
Chika
C
Yokota
Shuji
S
Takahashi
Makoto
M
Asashima
D000818:Animals; D001483:Base Sequence; D005260:Female; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D055458:Left-Right Determination Factors; D008648:Mesoderm / Q000187:drug effects; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010641:Phenotype; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014981:Xenopus / Q000196:embryology / Q000235:genetics / Q000502:physiology; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*
D036341:Intercellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D020319:Oligodeoxyribonucleotides, Antisense; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C492176:lefty protein, Xenopus