ABSTRACT
Wnt signaling pathways play essential roles in patterning and proliferation of embryonic and adult tissues. In many organisms, this signaling pathway directs axis formation. Although the importance of intracellular components of the pathway, including beta-catenin and Tcf3, has been established, the mechanism of their activation is uncertain. In Xenopus, the initiating signal that localizes beta-catenin to dorsal nuclei has been suggested to be intracellular and Wnt independent. Here, we provide three lines of evidence that the pathway specifying the dorsal axis is activated extracellularly in Xenopus embryos. First, we identify Wnt11 as the initiating signal. Second, we show that activation requires the glycosyl transferase X.EXT1. Third, we find that the EGF-CFC protein, FRL1, is also essential and interacts with Wnt11 to activate canonical Wnt signaling.
Subject(s)
Body Patterning/physiology , Cytoskeletal Proteins/metabolism , Glycoproteins/metabolism , Signal Transduction/physiology , Trans-Activators/metabolism , Xenopus/metabolism , Animals , Body Patterning/genetics , Cytoskeletal Proteins/genetics , DNA Primers/genetics , Embryo, Nonmammalian/metabolism , Female , GPI-Linked Proteins , Gene Expression Regulation, Developmental/genetics , Gene Expression Regulation, Developmental/physiology , Glycoproteins/genetics , Homeodomain Proteins/metabolism , Intercellular Signaling Peptides and Proteins , Membrane Proteins/metabolism , N-Acetylglucosaminyltransferases/metabolism , Oocytes/growth & development , Oocytes/metabolism , Protein Binding , RNA, Messenger/genetics , Signal Transduction/genetics , Trans-Activators/genetics , Transcription Factors/metabolism , Wnt Proteins , Xenopus/embryology , Xenopus Proteins/metabolism , beta CateninABSTRACT
FoxH1 (Fast1) was first characterized as the transcriptional partner for Smad proteins. Together with Smad2/4, it forms the activin response factor (ARF) that binds to the Mix.2 promoter in Xenopus embryos. Foxh1 is expressed maternally in Xenopus. Depletion of maternal Foxh1 mRNA results in abnormalities of head and dorsal axis formation. We show that FoxH1 is required, together with XTcf3/beta catenin, to activate the zygotic expression of the nodal gene, Xnr3 in a Smad2-independent manner. In contrast, maternal FoxH1 acts as an inhibitor of Xnr5 and 6 transcription, preventing their upregulation on the ventral side of the embryo, by the maternal T-box transcription factor VegT. We conclude that maternal FoxH1 has essential, context-dependent roles in regulating the pattern of zygotic gene expression in the early embryo.
