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XB-ART-3171
Int J Dev Biol 2004 Jun 01;484:275-83. doi: 10.1387/ijdb.041805kt.
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Xantivin suppresses the activity of EGF-CFC genes to regulate nodal signaling.



Abstract
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.

PubMed ID: 15300508
Article link: Int J Dev Biol


Species referenced: Xenopus
Genes referenced: actl6a chrd cripto.3 egf egr2 foxg1 gal.2 lefty mixer myod1 nodal nodal1 not ptpn11 tbxt wnt8a
Antibodies: FLAG Ab1 FLAG Ab2 HA Ab4 Notochord Ab1
Morpholinos: lefty MO3


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